Thiazole and Related Heterocyclic Systems as Anticancer Agents: A
Review on Synthetic Strategies, Mechanisms of Action and SAR Studies

Sahil; Kamalpreet      Kaur; Vikas      Jaitak
Abstract

Background: Cancer is the second leading cause of death worldwide. Many anticancer drugs are commercially available, but lack of selectivity, target specificity, cytotoxicity, and development of resistance lead to serious side effects. Several experiments have been going on to develop compounds with minor or no side effects.
Objective: This review mainly emphasizes synthetic strategies, SAR studies, and mechanism of action if thiazole, benzothiazole, and imidazothiazole-containing compounds as anticancer agents.
Methods: Recent literature related to thiazole and thiazole-related derivatives endowed with encouraging anticancer potential is reviewed. This review emphasizes contemporary strategies used for the synthesis of thiazole and related derivatives, mechanistic targets, and comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency thiazole-based anticancer drug candidates.
Results: Exhaustive literature survey indicated that thiazole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Thiazoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogenmediated activity. Furthermore, thiazole derivatives have been found to modulate critical targets, such as topoisomerase and HDAC.
Conclusion: Thiazole derivatives seem to be quite competent and act through various mechanisms. Some of the thiazole derivatives, such as compounds 29, 40, 62, and 74a with IC₅₀ values of 0.05 μM, 0.00042 μM, 0.18 μM, and 0.67 μM, respectively, not only exhibit anticancer activity, but they also have lower toxicity and better absorption. Therefore, some other similar compounds could be investigated to aid in the development of anticancer pharmacophores.
Keywords: Thiazoles, anticancer, synthesis, targets, SAR, molecular docking, resistance, heterocyclic systems.
[1] 
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin.,  2016, 66(1), 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID:  26742998] 
[2] 
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin.,  2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID:  31912902] 
[3] 
Dandriyal, J.; Singla, R.; Kumar, M.; Jaitak, V. Recent developments of C-4 substituted coumarin derivatives as anticancer agents. Eur. J. Med. Chem.,  2016, 119, 141-168.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.087] [PMID:  27155469] 
[4] 
Wayteck, L.; Breckpot, K.; Demeester, J.; De Smedt, S.C.; Raemdonck, K. A personalized view on cancer immunotherapy. Cancer Lett.,  2014, 352(1), 113-125.
[http://dx.doi.org/10.1016/j.canlet.2013.09.016] [PMID:  24051308] 
[5] 
He, X.; Li, X.Y.; Liang, J.W.; Cao, C.; Li, S.; Zhang, T.J.; Meng, F.H. Design, synthesis and anticancer activities evaluation of novel 5H-dibenzo[b,e]azepine-6,11-dione derivatives containing 1,3,4-oxadiazole units. Bioorg. Med. Chem. Lett.,  2018, 28(5), 847-852.
[http://dx.doi.org/10.1016/j.bmcl.2018.02.008] [PMID:  29456106] 
[6] 
Reddy, T.S.; Kulhari, H.; Reddy, V.G.; Bansal, V.; Kamal, A.; Shukla, R. Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents. Eur. J. Med. Chem.,  2015, 101, 790-805.
[http://dx.doi.org/10.1016/j.ejmech.2015.07.031] [PMID:  26231080] 
[7] 
Dhiman, N.; Kaur, K.; Jaitak, V. Tetrazoles as anticancer agents: A review on synthetic strategies, mechanism of action and SAR studies. Bioorg. Med. Chem.,  2020, 28(15), 115599.
[http://dx.doi.org/10.1016/j.bmc.2020.115599] [PMID:  32631569] 
[8] 
Dong, P.; Rakesh, K.P.; Manukumar, H.M.; Mohammed, Y.H.E.; Karthik, C.S.; Sumathi, S.; Mallu, P.; Qin, H-L. Innovative nano-carriers in anticancer drug delivery-a comprehensive review. Bioorg. Chem.,  2019, 85, 325-336.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.019] [PMID:  30658232] 
[9] 
Chhabria, M.T.; Patel, S.; Modi, P.; Brahmkshatriya, P.S. Thiazole: A review on chemistry, synthesis and therapeutic importance of its derivatives. Curr. Top. Med. Chem.,  2016, 16(26), 2841-2862.
[http://dx.doi.org/10.2174/1568026616666160506130731] [PMID:  27150376] 
[10] 
Zhang, X.; Rakesh, K.P.; Shantharam, C.S.; Manukumar, H.M.; Asiri, A.M.; Marwani, H.M.; Qin, H-L. Podophyllotoxin derivatives as an excellent anticancer aspirant for future chemotherapy: A key current imminent needs. Bioorg. Med. Chem.,  2018, 26(2), 340-355.
[http://dx.doi.org/10.1016/j.bmc.2017.11.026] [PMID:  29269253] 
[11] 
Fang, W-Y.; Ravindar, L.; Rakesh, K.P.; Manukumar, H.M.; Shantharam, C.S.; Alharbi, N.S.; Qin, H-L. Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review. Eur. J. Med. Chem.,  2019, 173, 117-153.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.063] [PMID:  30995567] 
[12] 
Moku, B.; Ravindar, L.; Rakesh, K.P.; Qin, H-L. The significance of N-methylpicolinamides in the development of anticancer therapeu-tics: Synthesis and structure-activity relationship (SAR) studies. Bioorg. Chem.,  2019, 86, 513-537.
[http://dx.doi.org/10.1016/j.bioorg.2019.02.030] [PMID:  30782571] 
[13] 
Zhao, C.; Rakesh, K.; Mumtaz, S.; Moku, B.; Asiri, A.M.; Marwani, H.M.; Manukumar, H.; Qin, H-L. Arylnaphthalene lactone ana-logues: Synthesis and development as excellent biological candidates for future drug discovery. RSC Advances,  2018, 8(17), 9487-9502.
[http://dx.doi.org/10.1039/C7RA13754K] 
[14] 
Zhao, C.; Rakesh, K.P.; Ravidar, L.; Fang, W-Y.; Qin, H-L. Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review. Eur. J. Med. Chem.,  2019, 162, 679-734.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.017] [PMID:  30496988] 
[15] 
Wang, M.; Rakesh, K.P.; Leng, J.; Fang, W-Y.; Ravindar, L.; Channe Gowda, D.; Qin, H-L. Amino acids/peptides conjugated heterocy-cles: A tool for the recent development of novel therapeutic agents. Bioorg. Chem.,  2018, 76, 113-129.
[http://dx.doi.org/10.1016/j.bioorg.2017.11.007] [PMID:  29169078] 
[16] 
Singh, I.P.; Gupta, S.; Kumar, S. Thiazole compounds as antiviral agents: An update. Med. Chem.,  2020, 16(1), 4-23.
[http://dx.doi.org/10.2174/1573406415666190614101253] [PMID:  31203807] 
[17] 
Bueno, J.M.; Carda, M.; Crespo, B.; Cuñat, A.C.; de Cozar, C.; León, M.L.; Marco, J.A.; Roda, N.; Sanz-Cervera, J.F. Design, synthe-sis and antimalarial evaluation of novel thiazole derivatives. Bioorg. Med. Chem. Lett.,  2016, 26(16), 3938-3944.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.010] [PMID:  27432764] 
[18] 
Kashyap, A.; Adhikari, N.; Das, A.; Shakya, A.; Ghosh, S.K.; Singh, U.P.; Bhat, H.R. Review on synthetic chemistry and antibacterial importance of thiazole derivatives. Curr. Drug Discov. Technol.,  2018, 15(3), 214-228.
[http://dx.doi.org/10.2174/1570163814666170911144036] [PMID:  28901248] 
[19] 
Ramprasad, J.; Nayak, N.; Dalimba, U.; Yogeeswari, P.; Sriram, D. Ionic liquid-promoted one-pot synthesis of thiazole–imidazo [2, 1-b][1, 3, 4] thiadiazole hybrids and their antitubercular activity. MedChemComm,  2016, 7(2), 338-344.
[http://dx.doi.org/10.1039/C5MD00346F] [PMID:  30108749] 
[20] 
Kryshchyshyn, A.; Atamanyuk, D.; Kaminskyy, D.; Grellier, P.; Lesyk, R. Investigation of anticancer and anti-parasitic activity of thi-opyrano [2, 3-d] thiazoles bearing norbornane moiety. Biopolim. Kletka,  2017, 33(3), 183-205.
[http://dx.doi.org/10.7124/bc.00094F] 
[21] 
Arora, P.; Narang, R.; Nayak, S.K.; Singh, S.K.; Judge, V. 2, 4-Disubstituted thiazoles as multitargated bioactive molecules. Med. Chem. Res.,  2016, 25(9), 1717-1743.
[http://dx.doi.org/10.1007/s00044-016-1610-2] 
[22] 
Lino, C.I.; Gonçalves de Souza, I.; Borelli, B.M.; Silvério Matos, T.T.; Santos Teixeira, I.N.; Ramos, J.P.; Maria de Souza Fagundes, E.; de Oliveira Fernandes, P.; Maltarollo, V.G.; Johann, S.; de Oliveira, R.B. Synthesis, molecular modeling studies and evaluation of antifungal activity of a novel series of thiazole derivatives. Eur. J. Med. Chem.,  2018, 151, 248-260.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.083] [PMID:  29626797] 
[23] 
Yapati, H.; Devineni, S.R.; Chirumamilla, S.; Kalluru, S. Synthesis, characterization and studies on antioxidant and molecular docking of metal complexes of 1-(benzo [d] thiazol-2-yl) thiourea. J. Chem. Sci.,  2016, 128(1), 43-51.
[http://dx.doi.org/10.1007/s12039-015-0999-3] 
[24] 
Ghabbour, H.A.; Kadi, A.A.; ElTahir, K.E.; Angawi, R.F.; El-Subbagh, H.I. Synthesis, biological evaluation and molecular docking studies of thiazole-based pyrrolidinones and isoindolinediones as anticonvulsant agents. Med. Chem. Res.,  2015, 24(8), 3194-3211.
[http://dx.doi.org/10.1007/s00044-015-1371-3] 
[25] 
Ayati, A.; Emami, S.; Asadipour, A.; Shafiee, A.; Foroumadi, A. Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. Eur. J. Med. Chem.,  2015, 97, 699-718.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.015] [PMID:  25934508] 
[26] 
Khlebnikova, T.; Panibrat, O.; Piven, Y.A.; Zinovich, V.; Tumar, E.; Ogurtsova, S.; Lakhvich, F. Cytotoxic activity of perfluoroalkyl-substituted imidazoindazoles and imidazobenzisoxazoles. Pharm. Chem. J.,  2021, 1-5(3), 219-223.
[http://dx.doi.org/10.1007/s11094-021-02401-4] 
[27] 
Ayati, A.; Emami, S.; Moghimi, S.; Foroumadi, A. Thiazole in the targeted anticancer drug discovery. Future Med. Chem.,  2019, 11(15), 1929-1952.
[http://dx.doi.org/10.4155/fmc-2018-0416] [PMID:  31313595] 
[28] 
Sharma, P.C.; Bansal, K.K.; Sharma, A.; Sharma, D.; Deep, A. Thiazole-containing compounds as therapeutic targets for cancer therapy. Eur. J. Med. Chem.,  2020, 188, 112016.
[http://dx.doi.org/10.1016/j.ejmech.2019.112016] [PMID:  31926469] 
[29] 
Wang, S-M.; Zha, G-F.; Rakesh, K.P.; Darshini, N.; Shubhavathi, T.; Vivek, H.K.; Mallesha, N.; Qin, H-L. Synthesis of ben-zo[d]thiazole-hydrazone analogues: Molecular docking and SAR studies of potential H+/K+ ATPase inhibitors and anti-inflammatory agents. MedChemComm,  2017, 8(6), 1173-1189.
[http://dx.doi.org/10.1039/C7MD00111H] [PMID:  30108827] 
[30] 
Zha, G-F.; Leng, J.; Darshini, N.; Shubhavathi, T.; Vivek, H.K.; Asiri, A.M.; Marwani, H.M.; Rakesh, K.P.; Mallesha, N.; Qin, H-L. Synthesis, SAR and molecular docking studies of benzo[d]thiazole-hydrazones as potential antibacterial and antifungal agents. Bioorg. Med. Chem. Lett.,  2017, 27(14), 3148-3155.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.032] [PMID:  28539243] 
[31] 
Tsai, C-Y.; Kapoor, M.; Huang, Y-P.; Lin, H-H.; Liang, Y-C.; Lin, Y-L.; Huang, S-C.; Liao, W-N.; Chen, J-K.; Huang, J-S.; Hsu, M.H. Synthesis and evaluation of aminothiazole-paeonol derivatives as potential anticancer agents. Molecules,  2016, 21(2), 145.
[http://dx.doi.org/10.3390/molecules21020145] [PMID:  26821004] 
[32] 
Sadeghzadeh, S.M.; Malekzadeh, M. Synthesis of 1, 3-thiazolidin-4-one using ionic liquid immobilized onto Fe3O4/SiO2/Salen/Mn. J. Mol. Liq.,  2015, 202, 46-51.
[http://dx.doi.org/10.1016/j.molliq.2014.12.011] 
[33] 
Khandelwal, S.; Tailor, Y.K.; Kumar, M. Deep eutectic solvents (DESs) as eco-friendly and sustainable solvent/catalyst systems in or-ganic transformations. J. Mol. Liq.,  2016, 215, 345-386.
[http://dx.doi.org/10.1016/j.molliq.2015.12.015] 
[34] 
Tiwari, J.; Singh, S.; Tufail, F.; Jaiswal, D.; Singh, J.; Singh, J. Glycerol micellar catalysis: An efficient multicomponent‐tandem green synthetic approach to biologically important 2, 4‐disubstituted thiazole derivatives. ChemistrySelect,  2018, 3(41), 11634-11642.
[http://dx.doi.org/10.1002/slct.201802511] 
[35] 
Safari, J.; Shokrani, Z.; Zarnegar, Z. Asparagine as a green organocatalyst for the synthesis of 2-aminothiazoles. Polycycl. Aromat. Compd.,  2020, 40(4), 1105-1111.
[http://dx.doi.org/10.1080/10406638.2018.1528287] 
[36] 
Raut, D.G.; Bhosale, R.B. One-pot PEG-mediated syntheses of 2-(2-hydrazinyl) thiazole derivatives: Novel route. J. Sulfur Chem.,  2018, 39(1), 1-7.
[http://dx.doi.org/10.1080/17415993.2017.1371175] 
[37] 
Beyzaei, H.; Aryan, R.; Molashahi, H.; Zahedi, M.M.; Samzadeh-Kermani, A.; Ghasemi, B.; Moghaddam-Manesh, M. MgO nanoparti-cle-catalyzed, solvent-free Hantzsch synthesis and antibacterial evaluation of new substituted thiazoles. J. Iran. Chem. Soc.,  2017, 14(5), 1023-1031.
[http://dx.doi.org/10.1007/s13738-017-1052-x] 
[38] 
Riyadh, S.M.; Khalil, K.D.; Aljuhani, A. Chitosan-MgO nanocomposite: One pot preparation and its utility as an ecofriendly biocatalyst in the synthesis of thiazoles and [1,3,4]thiadiazoles. Nanomaterials (Basel),  2018, 8(11), 928.
[http://dx.doi.org/10.3390/nano8110928] [PMID:  30413060] 
[39] 
Shaterian, H.R.; Molaei, P. Fe3O4@ vitamin B1 as a sustainable superparamagnetic heterogeneous nanocatalyst promoting green synthe-sis of trisubstituted 1, 3‐thiazole derivatives. Appl. Organomet. Chem.,  2019, 33(7), e4964.
[http://dx.doi.org/10.1002/aoc.4964] 
[40] 
Cheng, K.; McClory, A.; Walker, W.; Xu, J.; Zhang, H.; Angelaud, R.; Gosselin, F. A Strecker approach to 2-substituted ethyl 5-aminothiazole-4-carboxylates. Tetrahedron Lett.,  2016, 57(16), 1736-1738.
[http://dx.doi.org/10.1016/j.tetlet.2015.12.069] 
[41] 
Lauder, K.; Toscani, A.; Scalacci, N.; Castagnolo, D. Synthesis and reactivity of propargylamines in organic chemistry. Chem. Rev.,  2017, 117(24), 14091-14200.
[http://dx.doi.org/10.1021/acs.chemrev.7b00343] [PMID:  29166000] 
[42] 
Scalacci, N.; Pelloja, C.; Radi, M.; Castagnolo, D. Microwave-assisted domino reactions of propargylamines with isothiocyanates: Se-lective synthesis of 2-aminothiazoles and 2-amino-4-methylenethiazolines. Synlett,  2016, 27(12), 1883-1887.
[http://dx.doi.org/10.1055/s-0035-1561985] 
[43] 
Shinde, M.H.; Kshirsagar, U.A. One pot synthesis of substituted imidazopyridines and thiazoles from styrenes in water assisted by NBS. Green Chem.,  2016, 18(6), 1455-1458.
[http://dx.doi.org/10.1039/C5GC02771C] 
[44] 
Babar, A.; Khalid, H.; Ayub, K.; Saleem, S.; Waseem, A.; Mahmood, T.; Munawar, M.A.; Abbas, G.; Khan, A.F. Synthesis, characteri-zation and density functional theory study of some new 2-anilinothiazoles. J. Mol. Struct.,  2014, 1072, 221-227.
[http://dx.doi.org/10.1016/j.molstruc.2014.05.009] 
[45] 
Mallia, C.J.; Englert, L.; Walter, G.C.; Baxendale, I.R. Thiazole formation through a modified Gewald reaction. Beilstein J. Org. Chem.,  2015, 11(1), 875-883.
[http://dx.doi.org/10.3762/bjoc.11.98] [PMID:  26124889] 
[46] 
Xiabing, M.; Ablajan, K.; Obul, M.; Seydimemet, M.; Ruzi, R.; Wenbo, L. Facial one-pot, three-component synthesis of thiazole com-pounds by the reactions of aldehyde/ketone, thiosemicarbazide and chlorinated carboxylic ester derivatives. Tetrahedron,  2016, 72(18), 2349-2353.
[http://dx.doi.org/10.1016/j.tet.2016.03.053] 
[47] 
Pathak, N.; Rathi, E.; Kumar, N.; Kini, S.G.; Rao, C.M. A review on anticancer potentials of benzothiazole derivatives. Mini Rev. Med. Chem.,  2020, 20(1), 12-23.
[http://dx.doi.org/10.2174/1389557519666190617153213] [PMID:  31288719] 
[48] 
Gao, X.; Liu, J.; Zuo, X.; Feng, X.; Gao, Y. Recent advances in synthesis of benzothiazole compounds related to green chemistry. Molecules,  2020, 25(7), 1675.
[http://dx.doi.org/10.3390/molecules25071675] [PMID:  32260500] 
[49] 
Ye, L.; Chen, J.; Mao, P.; Mao, Z.; Zhang, X.; Yan, M. Visible-light-promoted synthesis of benzothiazoles from 2-aminothiophenols and aldehydes. Tetrahedron Lett.,  2017, 58(9), 874-876.
[http://dx.doi.org/10.1016/j.tetlet.2017.01.053] 
[50] 
Maphupha, M.; Juma, W.P.; de Koning, C.B.; Brady, D. A modern and practical laccase-catalysed route suitable for the synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles. RSC Advances,  2018, 8(69), 39496-39510.
[http://dx.doi.org/10.1039/C8RA07377E] 
[51] 
Merroun, Y.; Chehab, S.; Ghailane, T.; Akhazzane, M.; Souizi, A.; Ghailane, R. Preparation of tin-modified mono-ammonium phos-phate fertilizer and its application as heterogeneous catalyst in the benzimidazoles and benzothiazoles synthesis. React. Kinet. Mech. Catal.,  2019, 126(1), 249-264.
[http://dx.doi.org/10.1007/s11144-018-1446-5] 
[52] 
Bhat, R.; Karhale, S.; Arde, S.; Helavi, V. Acacia concinna pod catalyzed synthesis of 2-arylbenzothia/(oxa) zole derivatives. Iran. J. Catal.,  2019, 9(2), 173-179.http://ijc.iaush.ac.ir/article_664816.html
[53] 
Ghafuri, H.; Esmaili, E.; Talebi, M. Fe3O4@ SiO2/collagen: An efficient magnetic nanocatalyst for the synthesis of benzimidazole and benzothiazole derivatives. C. R. Chim.,  2016, 19(8), 942-950.
[http://dx.doi.org/10.1016/j.crci.2016.05.003] 
[54] 
Kumar, P.; Bhatia, R.; Khanna, R.; Dalal, A.; Kumar, D.; Surain, P.; Kamboj, R.C. Synthesis of some benzothiazoles by developing a new protocol using urea nitrate as a catalyst and their antimicrobial activities. J. Sulfur Chem.,  2017, 38(6), 585-596.
[http://dx.doi.org/10.1080/17415993.2017.1334781] 
[55] 
Kan, S-Y.; Yiong, W.S.; Yong, F.S.J.; Chia, P.W. Synthesis of benzothiazole derivatives using ultrasonic probe irradiation. Malays. J. Anal. Sci.,  2017, 21(6), 1219-1225.
[http://dx.doi.org/10.17576/mjas-2017-2106-02] 
[56] 
Hwang, H.S.; Lee, S.; Han, S.S.; Moon, Y.K.; You, Y.; Cho, E.J. Benzothiazole synthesis: Mechanistic investigation of an in situ-generated photosensitizing disulfide. J. Org. Chem.,  2020, 85(18), 11835-11843.
[http://dx.doi.org/10.1021/acs.joc.0c01598] [PMID:  32822174] 
[57] 
Sankar, V.; Karthik, P.; Neppolian, B.; Sivakumar, B. Metal–organic framework mediated expeditious synthesis of benzimidazole and benzothiazole derivatives through an oxidative cyclization pathway. New J. Chem.,  2020, 44(3), 1021-1027.
[http://dx.doi.org/10.1039/C9NJ04431K] 
[58] 
Dar, A.A.; Shadab, M.; Khan, S.; Ali, N.; Khan, A.T. One-pot synthesis and evaluation of antileishmanial activities of functionalized S-alkyl/aryl benzothiazole-2-carbothioate scaffold. J. Org. Chem.,  2016, 81(8), 3149-3160.
[http://dx.doi.org/10.1021/acs.joc.6b00113] [PMID:  26999637] 
[59] 
Luo, B.; Li, D.; Zhang, A-L.; Gao, J-M. Synthesis, antifungal activities and molecular docking studies of benzoxazole and benzothiazole derivatives. Molecules,  2018, 23(10), 2457.
[http://dx.doi.org/10.3390/molecules23102457] [PMID:  30257495] 
[60] 
Folgueiras-Amador, A.A.; Qian, X-Y.; Xu, H.C.; Wirth, T. Catalyst-and supporting electrolyte-free electrosynthesis of benzothiazoles and thiazolopyridines in continuousf flow. Chemistry,  2018, 24(2), 487-491.
[http://dx.doi.org/10.1002/chem.201705016] [PMID:  29125202] 
[61] 
Xu, Z-M.; Li, H-X.; Young, D.J.; Zhu, D-L.; Li, H-Y.; Lang, J-P. Exogenous photosensitizer-, metal-, and base-free visible-light-promoted C–H thiolation via reverse hydrogen atom transfer. Org. Lett.,  2019, 21(1), 237-241.
[http://dx.doi.org/10.1021/acs.orglett.8b03679] [PMID:  30575402] 
[62] 
Bouchet, L.M.; Heredia, A.A.; Argüello, J.E.; Schmidt, L.C. Riboflavin as photoredox catalyst in the cyclization of thiobenzanilides: Synthesis of 2-substituted benzothiazoles. Org. Lett.,  2020, 22(2), 610-614.
[http://dx.doi.org/10.1021/acs.orglett.9b04384] [PMID:  31887062] 
[63] 
Gao, X.; Yu, B.; Yang, Z.; Zhao, Y.; Zhang, H.; Hao, L.; Han, B.; Liu, Z. Ionic liquid-catalyzed C–S bond construction using CO2 as a C1 building block under mild conditions: A metal-free route to synthesis of benzothiazoles. ACS Catal.,  2015, 5(11), 6648-6652.
[http://dx.doi.org/10.1021/acscatal.5b01874] 
[64] 
Chun, S.; Yang, S.; Chung, Y.K. Synthesis of benzothiazoles from 2-aminobenzenethiols in the presence of a reusable polythiazolium precatalyst under atmospheric pressure of carbon dioxide. Tetrahedron,  2017, 73(25), 3438-3442.
[http://dx.doi.org/10.1016/j.tet.2017.05.003] 
[65] 
Monga, A.; Bagchi, S.; Soni, R.K.; Sharma, A. Synthesis of benzothiazoles via photooxidative decarboxylation of α‐keto acids. Adv. Synth. Catal.,  2020, 362(11), 2232-2237.
[http://dx.doi.org/10.1002/adsc.201901617] 
[66] 
Kazi, I.; Sekar, G. An efficient synthesis of benzothiazole using tetrabromomethane as a halogen bond donor catalyst. Org. Biomol. Chem.,  2019, 17(45), 9743-9756.
[http://dx.doi.org/10.1039/C9OB02125F] [PMID:  31696198] 
[67] 
Liu, B.; Zhu, N.; Hong, H.; Han, L. Novel synthesis of benzothiazole by self-redox tandem reaction of disulfide with aldehyde. Tetrahedron,  2015, 71(49), 9287-9292.
[http://dx.doi.org/10.1016/j.tet.2015.10.029] 
[68] 
Zhao, J.; Xiao, Q.; Chen, J. Xu, J. Metal‐free synthesis of imidazo [2, 1‐b] thiazoles from thioimidazoles and ketones mediated by selectfluor. Eur. J. Org. Chem.,  2020, 2020(32), 5201-5206.
[http://dx.doi.org/10.1002/ejoc.202000815] 
[69] 
Mishra, A.; Srivastava, M.; Rai, P.; Yadav, S.; Tripathi, B.P.; Singh, J.; Singh, J. Visible light triggered, catalyst free approach for the synthesis of thiazoles and imidazo [2, 1-b] thiazoles in EtOH: H2O green medium. RSC Advances,  2016, 6(54), 49164-49172.
[http://dx.doi.org/10.1039/C6RA05385H] 
[70] 
Vekariya, R.H.; Patel, K.D.; Vekariya, M.K.; Prajapati, N.P.; Rajani, D.P.; Rajani, S.D.; Patel, H.D. Microwave-assisted green synthesis of new imidazo [2, 1-b] thiazole derivatives and their antimicrobial, antimalarial, and antitubercular activities. Res. Chem. Intermed.,  2017, 43(11), 6207-6231.
[http://dx.doi.org/10.1007/s11164-017-2985-5] 
[71] 
Chen, Z.; Jin, W.; Xia, Y.; Zhang, Y.; Xie, M.; Ma, S.; Liu, C. Aminothiolation of α-Bromocinnamaldehydes to access Imidazo[2,1-b]thiazoles by incorporation of two distinct Photoinduced processes. Org. Lett.,  2020, 22(21), 8261-8266.
[http://dx.doi.org/10.1021/acs.orglett.0c02907] [PMID:  33021794] 
[72] 
Mukku, N.; Maiti, B. On water catalyst-free synthesis of benzo [d] imidazo [2, 1-b] thiazoles and novel N-alkylated 2-aminobenzo [d] oxazoles under microwave irradiation. RSC Advances,  2020, 10(2), 770-778.
[http://dx.doi.org/10.1039/C9RA08929B] 
[73] 
Balwe, S.G.; Jeong, Y.T. Iron-catalyzed unprecedented formation of benzo [d] imidazo [2, 1-b] thiazoles under solvent-free conditions. RSC Advances,  2016, 6(109), 107225-107232.
[http://dx.doi.org/10.1039/C6RA24183B] 
[74] 
Neganova, M.E.; Klochkov, S.G.; Aleksandrova, Y.R.; Aliev, G. Histone modifications in epigenetic regulation of
 cancer: Perspectives and achieved progress. Semin. Cancer Biol., 2020. S1044-579X(20)30176-0
[http://dx.doi.org/10.1016/j.semcancer.2020.07.015] [PMID: 32814115] 
[75] 
Rajak, H.; Singh, A.; Raghuwanshi, K.; Kumar, R.; Dewangan, P.K.; Veerasamy, R.; Sharma, P.C.; Dixit, A.; Mishra, P. A structural insight into hydroxamic acid based histone deacetylase inhibitors for the presence of anticancer activity. Curr. Med. Chem.,  2014, 21(23), 2642-2664.
[http://dx.doi.org/10.2174/09298673113209990191] [PMID:  23895688] 
[76] 
Carradori, S.; Rotili, D.; De Monte, C.; Lenoci, A.; D’Ascenzio, M.; Rodriguez, V.; Filetici, P.; Miceli, M.; Nebbioso, A.; Altucci, L.; Secci, D.; Mai, A. Evaluation of a large library of (thiazol-2-yl)hydrazones and analogues as histone acetyltransferase inhibitors: Enzyme and cellular studies. Eur. J. Med. Chem.,  2014, 80, 569-578.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.042] [PMID:  24835815] 
[77] 
Secci, D.; Carradori, S.; Bizzarri, B.; Bolasco, A.; Ballario, P.; Patramani, Z.; Fragapane, P.; Vernarecci, S.; Canzonetta, C.; Filetici, P. Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors. Bioorg. Med. Chem.,  2014, 22(5), 1680-1689.
[http://dx.doi.org/10.1016/j.bmc.2014.01.022] [PMID:  24513187] 
[78] 
Pardo-Jiménez, V.; Navarrete-Encina, P.; Díaz-Araya, G. Synthesis and biological evaluation of novel thiazolyl-coumarin derivatives as potent histone deacetylase inhibitors with antifibrotic activity. Molecules,  2019, 24(4), 739.
[http://dx.doi.org/10.3390/molecules24040739] [PMID:  30791388] 
[79] 
Zhang, S-W.; Gong, C-J.; Su, M-B.; Chen, F.; He, T.; Zhang, Y-M.; Shen, Q-Q.; Su, Y.; Ding, J.; Li, J.; Chen, Y.; Nan, F.J. Synthesis and in vitro and in vivo biological evaluation of tissue-specific bisthiazole Histone Deacetylase (HDAC) inhibitors. J. Med. Chem.,  2020, 63(2), 804-815.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01792] [PMID:  31855601] 
[80] 
Sarkar, R.; Banerjee, S.; Amin, S.A.; Adhikari, N.; Jha, T. Histone deacetylase 3 (HDAC3) inhibitors as anticancer agents: A review. Eur. J. Med. Chem.,  2020, 192, 112171.
[http://dx.doi.org/10.1016/j.ejmech.2020.112171] [PMID:  32163814] 
[81] 
Anh, D.T.; Hai, P-T.; Huong, L.T.; Park, E.J.; Jun, H.W.; Kang, J.S.; Kwon, J.H.; Dung, D.T.M.; Anh, V.T.; Hue, V.T.M.; Han, S.B.; Nam, N.H. Exploration of certain 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents. Bioorg. Chem.,  2020, 101, 103988.
[http://dx.doi.org/10.1016/j.bioorg.2020.103988] [PMID:  32534346] 
[82] 
Roostalu, J.; Surrey, T. Microtubule nucleation: Beyond the template. Nat. Rev. Mol. Cell Biol.,  2017, 18(11), 702-710.
[http://dx.doi.org/10.1038/nrm.2017.75] [PMID:  28831203] 
[83] 
Kaur, R.; Kaur, G.; Gill, R.K.; Soni, R.; Bariwal, J. Recent developments in tubulin polymerization inhibitors: An overview. Eur. J. Med. Chem.,  2014, 87, 89-124.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.051] [PMID:  25240869] 
[84] 
Naaz, F.; Haider, M.R.; Shafi, S.; Yar, M.S. Anti-tubulin agents of natural origin: Targeting taxol, vinca, and colchicine binding do-mains. Eur. J. Med. Chem.,  2019, 171, 310-331.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.025] [PMID:  30953881] 
[85] 
Subba Rao, A.V.; Swapna, K.; Shaik, S.P.; Lakshma Nayak, V.; Srinivasa Reddy, T.; Sunkari, S.; Shaik, T.B.; Bagul, C.; Kamal, A. Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymer-ization inhibitors and apoptosis inducers. Bioorg. Med. Chem.,  2017, 25(3), 977-999.
[http://dx.doi.org/10.1016/j.bmc.2016.12.010] [PMID:  28034647] 
[86] 
Ansari, M.; Shokrzadeh, M.; Karima, S.; Rajaei, S.; Fallah, M.; Ghassemi-Barghi, N.; Ghasemian, M.; Emami, S. New thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyph-enyl) moiety as anticancer agents. Eur. J. Med. Chem.,  2020, 185, 111784.
[http://dx.doi.org/10.1016/j.ejmech.2019.111784] [PMID:  31669850] 
[87] 
El-Naggar, A.M.; Eissa, I.H.; Belal, A.; El-Sayed, A.A. Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5 (4 H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site. RSC Advances,  2020, 10(5), 2791-2811.
[http://dx.doi.org/10.1039/C9RA10094F] 
[88] 
Guggilapu, S.D.; Guntuku, L.; Reddy, T.S.; Nagarsenkar, A.; Sigalapalli, D.K.; Naidu, V.G.M.; Bhargava, S.K.; Bathini, N.B. Synthe-sis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors. Eur. J. Med. Chem.,  2017, 138, 83-95.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.025] [PMID:  28648953] 
[89] 
Fu, D-J.; Liu, S-M.; Li, F-H.; Yang, J-J.; Li, J. Antiproliferative benzothiazoles incorporating a trimethoxyphenyl scaffold as novel col-chicine site tubulin polymerisation inhibitors. J. Enzyme Inhib. Med. Chem.,  2020, 35(1), 1050-1059.
[http://dx.doi.org/10.1080/14756366.2020.1753721] [PMID:  32299262] 
[90] 
Baig, M.F.; Nayak, V.L.; Budaganaboyina, P.; Mullagiri, K.; Sunkari, S.; Gour, J.; Kamal, A. Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents. Bioorg. Chem.,  2018, 77, 515-526.
[http://dx.doi.org/10.1016/j.bioorg.2018.02.005] [PMID:  29459129] 
[91] 
Shaik, S.P.; Nayak, V.L.; Sultana, F.; Rao, A.V.S.; Shaik, A.B.; Babu, K.S.; Kamal, A. Design and synthesis of imidazo[2,1-b]thiazole linked triazole conjugates: Microtubule-destabilizing agents. Eur. J. Med. Chem.,  2017, 126, 36-51.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.060] [PMID:  27744185] 
[92] 
Shaik, S.P.; Vishnuvardhan, M.V.P.S.; Sultana, F.; Subba Rao, A.V.; Bagul, C.; Bhattacharjee, D.; Kapure, J.S.; Jain, N.; Kamal, A. Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors. Bioorg. Med. Chem.,  2017, 25(13), 3285-3297.
[http://dx.doi.org/10.1016/j.bmc.2017.04.013] [PMID:  28462842] 
[93] 
Sultana, F.; Reddy Bonam, S.; Reddy, V.G.; Nayak, V.L.; Akunuri, R.; Rani Routhu, S.; Alarifi, A.; Halmuthur, M.S.K.; Kamal, A. Synthesis of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates as microtubule targeting and apoptosis inducing agents. Bioorg. Chem.,  2018, 76, 1-12.
[http://dx.doi.org/10.1016/j.bioorg.2017.10.019] [PMID:  29102724] 
[94] 
Sigismund, S.; Avanzato, D.; Lanzetti, L. Emerging functions of the EGFR in cancer. Mol. Oncol.,  2018, 12(1), 3-20.
[http://dx.doi.org/10.1002/1878-0261.12155] [PMID:  29124875] 
[95] 
Feng, Y.; Spezia, M.; Huang, S.; Yuan, C.; Zeng, Z.; Zhang, L.; Ji, X.; Liu, W.; Huang, B.; Luo, W.; Liu, B.; Lei, Y.; Du, S.; Vuppala-pati, A.; Luu, H.H.; Haydon, R.C.; He, T.C.; Ren, G. Breast cancer development and progression: Risk factors, cancer stem cells, signal-ing pathways, genomics, and molecular pathogenesis. Genes Dis.,  2018, 5(2), 77-106.
[http://dx.doi.org/10.1016/j.gendis.2018.05.001] [PMID:  30258937] 
[96] 
Minder, P.; Zajac, E.; Quigley, J.P.; Deryugina, E.I. EGFR regulates the development and microarchitecture of intratumoral angiogenic vasculature capable of sustaining cancer cell intravasation. Neoplasia,  2015, 17(8), 634-649.
[http://dx.doi.org/10.1016/j.neo.2015.08.002] [PMID:  26408256] 
[97] 
Mohareb, R.M.; Abdo, N.Y.M.; Wardakhan, W.W. Synthesis and evaluation of pyrazolo [5, 1-b] quinazoline-2-carboxylate, and its thiazole derivatives as potential antiproliferative agents and Pim-1 kinase inhibitors. Med. Chem. Res.,  2017, 26(10), 2520-2537.
[http://dx.doi.org/10.1007/s00044-017-1951-5] 
[98] 
Sever, B. Altıntop, M.D.; Radwan, M.O.; Özdemir, A.; Otsuka, M.; Fujita, M.; Ciftci, H.I. Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors. Eur. J. Med. Chem.,  2019, 182, 111648.
[http://dx.doi.org/10.1016/j.ejmech.2019.111648] [PMID:  31493743] 
[99] 
Srour, A.M.; Ahmed, N.S.; Abd El-Karim, S.S.; Anwar, M.M.; El-Hallouty, S.M. Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors. Bioorg. Med. Chem.,  2020, 28(18), 115657.
[http://dx.doi.org/10.1016/j.bmc.2020.115657] [PMID:  32828424] 
[100] 
Mahapatra, D.K.; Das, D.; Shivhare, R. Substituted thiazole linked murrayanine-Schiff’s base derivatives as potential anti-breast cancer candidates: Future EGFR Kinase inhibitors. Int. J. Pharm. Sci. Drug Res.,  2017, 9(3), 139-144.
[http://dx.doi.org/10.25004/IJPSDR.2017.090307] 
[101] 
Gabr, M.T.; El-Gohary, N.S.; El-Bendary, E.R.; El-Kerdawy, M.M. EGFR tyrosine kinase targeted compounds: In vitro antitumor activ-ity and molecular modeling studies of new benzothiazole and pyrimido[2,1-b]benzothiazole derivatives. EXCLI J.,  2014, 13, 573-585.
[PMID: 26417284] 
[102] 
Zhang, L.; Deng, X-S.; Zhang, C.; Meng, G-P.; Wu, J-F.; Li, X-S.; Zhao, Q-C.; Hu, C. Design, synthesis and cytotoxic evaluation of a novel series of benzo [d] thiazole-2-carboxamide derivatives as potential EGFR inhibitors. Med. Chem. Res.,  2017, 26(9), 2180-2189.
[http://dx.doi.org/10.1007/s00044-017-1925-7] 
[103] 
Labib, M.B.; Philoppes, J.N.; Lamie, P.F.; Ahmed, E.R. Azole-hydrazone derivatives: Design, synthesis, in vitro biological evaluation, dual EGFR/HER2 inhibitory activity, cell cycle analysis and molecular docking study as anticancer agents. Bioorg. Chem.,  2018, 76, 67-80.
[http://dx.doi.org/10.1016/j.bioorg.2017.10.016] [PMID:  29153588] 
[104] 
Abdellatif, K.R.A.; Belal, A.; El-Saadi, M.T.; Amin, N.H.; Said, E.G.; Hemeda, L.R. Design, synthesis, molecular docking and antipro-liferative activity of some novel benzothiazole derivatives targeting EGFR/HER2 and TS. Bioorg. Chem.,  2020, 101, 103976.
[http://dx.doi.org/10.1016/j.bioorg.2020.103976] [PMID:  32506018] 
[105] 
Asati, V.; Mahapatra, D.K.; Bharti, S.K. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur. J. Med. Chem.,  2016, 109, 314-341.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.012] [PMID:  26807863] 
[106] 
Corcoran, R.B.; Dias-Santagata, D.; Bergethon, K.; Iafrate, A.J.; Settleman, J.; Engelman, J.A. BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci. Signal.,  2010, 3(149), ra84-ra84.
[http://dx.doi.org/10.1126/scisignal.2001148] [PMID:  21098728] 
[107] 
Zhao, M-Y.; Yin, Y.; Yu, X-W.; Sangani, C.B.; Wang, S-F.; Lu, A-M.; Yang, L-F.; Lv, P-C.; Jiang, M-G.; Zhu, H-L. Synthesis, bio-logical evaluation and 3D-QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAF(V600E) inhibitors. Bioorg. Med. Chem.,  2015, 23(1), 46-54.
[http://dx.doi.org/10.1016/j.bmc.2014.11.029] [PMID:  25496804] 
[108] 
Abdel-Maksoud, M.S.; Kim, M-R.; El-Gamal, M.I.; Gamal El-Din, M.M.; Tae, J.; Choi, H.S.; Lee, K-T.; Yoo, K.H.; Oh, C-H. Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1-b]thiazole derivatives. Eur. J. Med. Chem.,  2015, 95, 453-463.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.065] [PMID:  25841200] 
[109] 
Abdel-Maksoud, M.S.; Ammar, U.M.; Oh, C-H. Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold. Bioorg. Med. Chem.,  2019, 27(10), 2041-2051.
[http://dx.doi.org/10.1016/j.bmc.2019.03.062] [PMID:  30955995] 
[110] 
Ammar, U.M.; Abdel-Maksoud, M.S.; Mersal, K.I.; Ali, E.M.H.; Yoo, K.H.; Choi, H.S.; Lee, J.K.; Cha, S.Y.; Oh, C-H. Modification of imidazothiazole derivatives gives promising activity in B-Raf kinase enzyme inhibition; synthesis, in vitro studies and molecular dock-ing. Bioorg. Med. Chem. Lett.,  2020, 30(20), 127478.
[http://dx.doi.org/10.1016/j.bmcl.2020.127478] [PMID:  32781217] 
[111] 
Yu, C-C.; Hung, S-K.; Lin, H-Y.; Chiou, W-Y.; Lee, M-S.; Liao, H-F.; Huang, H-B.; Ho, H-C.; Su, Y-C. Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinoma in vitro and in vivo. Oncotarget,  2017, 8(40), 68641-68653.
[http://dx.doi.org/10.18632/oncotarget.19817] [PMID:  28978144] 
[112] 
Khorami, S.A.H.; Movahedi, A.; Huzwah, K.; Sokhini, A. PI3K/AKT pathway in modulating glucose homeostasis and its alteration in diabetes. Ann. Med. Biomed. Sci.,  2015, 1(2), 46-55.http://ambs-journal.co.uk/articles/8%20AMBS46-55-20151.pdf
[113] 
Liu, Y.; Wan, W.Z.; Li, Y.; Zhou, G.L.; Liu, X.G. Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents. Oncotarget,  2017, 8(4), 7181-7200.
[http://dx.doi.org/10.18632/oncotarget.12742] [PMID:  27769061] 
[114] 
Altıntop, M.D.; Sever, B.; Akalın Çiftçi, G.; Özdemir, A. Design, synthesis, and evaluation of a new series of thiazole-based anticancer agents as potent Akt inhibitors. Molecules,  2018, 23(6), 1318.
[http://dx.doi.org/10.3390/molecules23061318] [PMID:  29857484] 
[115] 
Jin, R-Y.; Tang, T.; Zhou, S.; Long, X.; Guo, H.; Zhou, J.; Yan, H.; Li, Z.; Zuo, Z-Y.; Xie, H-L.; Tang, Y.P. Design, synthesis, anti-tumor activity and theoretical calculation of novel PI3Ka inhibitors. Bioorg. Chem.,  2020, 98, 103737.
[http://dx.doi.org/10.1016/j.bioorg.2020.103737] [PMID:  32193031] 
[116] 
Chen, N-Y.; Xie, Y-L.; Lu, G-D.; Ye, F.; Li, X-Y.; Huang, Y-W.; Huang, M-L.; Chen, T-Y.; Li, C-P. Synthesis and antitumor evalua-tion of (aryl) methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole as potential PI3K/AKT/mTOR signaling pathway inhibitors. Mol. Divers.,  2021, 25(2), 967-979.
[http://dx.doi.org/10.1007/s11030-020-10081-7] [PMID:  32297120] 
[117] 
Li, H.; Wang, X-M.; Wang, J.; Shao, T.; Li, Y-P.; Mei, Q-B.; Lu, S-M.; Zhang, S-Q. Combination of 2-methoxy-3-phenylsulfonylaminobenzamide and 2-aminobenzothiazole to discover novel anticancer agents. Bioorg. Med. Chem.,  2014, 22(14), 3739-3748.
[http://dx.doi.org/10.1016/j.bmc.2014.04.064] [PMID:  24878359] 
[118] 
Cao, S.; Cao, R.; Liu, X.; Luo, X.; Zhong, W. Design, synthesis and biological evaluation of novel benzothiazole derivatives as selective PI3Kβ inhibitors. Molecules,  2016, 21(7), 876.
[http://dx.doi.org/10.3390/molecules21070876] [PMID:  27384552] 
[119] 
Xie, L.; Huang, J.; Chen, X.; Yu, H.; Li, K.; Yang, D.; Chen, X.; Ying, J.; Pan, F.; Lv, Y.; Cheng, Y. Design, synthesis and biological evaluation of novel rapamycin benzothiazole hybrids as mTOR targeted anti-cancer agents. Chem. Pharm. Bull. (Tokyo),  2016, 64(4), 346-355.
[http://dx.doi.org/10.1248/cpb.c15-01016] [PMID:  26842804] 
[120] 
Altıntop, M.D.; Sever, B.; Akalın Çiftçi, G.; Turan-Zitouni, G.; Kaplancıklı Z.A.; Özdemir, A. Design, synthesis, in vitro and in silico evaluation of a new series of oxadiazole-based anticancer agents as potential Akt and FAK inhibitors. Eur. J. Med. Chem.,  2018, 155, 905-924.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.049] [PMID:  29966916] 
[121] 
Ratre, P.; Mishra, K.; Dubey, A.; Vyas, A.; Jain, A.; Thareja, S. Aromatase inhibitors for the treatment of breast cancer: A journey from the scratch. Anticancer. Agents Med. Chem.,  2020, 20(17), 1994-2004.
[http://dx.doi.org/10.2174/1871520620666200627204105] [PMID:  32593281] 
[122] 
Mohammed, S.A.; Hassan, F.; Philip, A.K.; Abd-Allateef, M.; Yousif, E. Role of aromatase and anastrozole in cancer treatment. Int. J. Pharm. Sci. Rev. Res.,  2016, 40, 135-140.https://www.researchgate.net/publication/316364530
[123] 
Sahin, Z.; Ertas, M.; Berk, B.; Biltekin, S.N.; Yurttas, L.; Demirayak, S. Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives. Bioorg. Med. Chem.,  2018, 26(8), 1986-1995.
[http://dx.doi.org/10.1016/j.bmc.2018.02.048] [PMID:  29525337] 
[124] 
Ertas, M.; Sahin, Z.; Berk, B.; Yurttas, L.; Biltekin, S.N.; Demirayak, S. Pyridine-substituted thiazolylphenol derivatives: Synthesis, modeling studies, aromatase inhibition, and antiproliferative activity evaluation. Arch. Pharm. (Weinheim),  2018, 351(3-4), e1700272.
[http://dx.doi.org/10.1002/ardp.201700272] [PMID:  29522642] 
[125] 
Ghorab, M.M.; Alsaid, M.S.; Samir, N.; Abdel-Latif, G.A.; Soliman, A.M.; Ragab, F.A.; Abou El Ella, D.A. Aromatase inhibitors and apoptotic inducers: Design, synthesis, anticancer activity and molecular modeling studies of novel phenothiazine derivatives carrying sul-fonamide moiety as hybrid molecules. Eur. J. Med. Chem.,  2017, 134, 304-315.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.028] [PMID:  28427017] 
[126] 
Çevik, U.A.; Osmaniye, D.; Levent, S. Sağlik, B.N.; Çavuşoğlu, B.K.; Karaduman, A.B.; Özkay, Y.; Kaplancikli, Z.A. Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as possible anticancer agents. Acta Pharm.,  2020, 70(4), 499-513.
[http://dx.doi.org/10.2478/acph-2020-0034] [PMID:  32412436] 
[127] 
Capranico, G.; Marinello, J.; Chillemi, G. Type I DNA Topoisomerases. J. Med. Chem.,  2017, 60(6), 2169-2192.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00966] [PMID:  28072526] 
[128] 
Madabhushi, R. The roles of DNA topoisomerase IIβ in transcription. Int. J. Mol. Sci.,  2018, 19(7), 1917.
[http://dx.doi.org/10.3390/ijms19071917] [PMID:  29966298] 
[129] 
Sankara Rao, N.; Nagesh, N.; Lakshma Nayak, V.; Sunkari, S.; Tokala, R.; Kiranmai, G.; Regur, P.; Shankaraiah, N.; Kamal, A. Design and synthesis of DNA-intercalative naphthalimide-benzothiazole/cinnamide derivatives: Cytotoxicity evaluation and topoisomerase-IIα inhibition. MedChemComm,  2018, 10(1), 72-79.
[http://dx.doi.org/10.1039/C8MD00395E] [PMID:  30774856] 
[130] 
Coman, F-M.; Mbaveng, A.T.; Marc, G.; Leonte, D.; Brém, B.; Vlase, L.; Imre, S.; Kuete, V.; Zaharia, V. Heterocycles 47. Synthesis, characterization and biological evaluation of some new thiazole aurones as antiproliferative agents. Farmacia,  2019, 68(3), 492-506.
[http://dx.doi.org/10.31925/farmacia.2020.3.15] 
[131] 
Keri, R.S.; Patil, M.R.; Patil, S.A.; Budagumpi, S. A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem.,  2015, 89, 207-251.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.059] [PMID:  25462241] 
[132] 
Aki-Yalcin, E.; Ertan-Bolelli, T.; Taskin-Tok, T.; Ozturk, O.; Ataei, S.; Ozen, C.; Yildiz, I.; Yalcin, I. Evaluation of inhibitory effects of benzothiazole and 3-amino-benzothiazolium derivatives on DNA topoisomerase II by molecular modeling studies. SAR QSAR Environ. Res.,  2014, 25(8), 637-649.
[http://dx.doi.org/10.1080/1062936X.2014.923039] [PMID:  25027467] 
[133] 
Lisic, E.C.; Rand, V.G.; Ngo, L.; Kent, P.; Rice, J.; Gerlach, D.; Papish, E.T.; Jiang, X. Cu (II) propionyl-thiazole thiosemicarbazone complexes: Crystal structure, inhibition of human topoisomerase IIα and activity against breast cancer cells. Open J. Med. Chem.,  2018, 8(2), 30-46.
[http://dx.doi.org/10.4236/ojmc.2018.82004] 
[134] 
Pfeffer, C.M.; Singh, A.T.K. Apoptosis: A target for anticancer therapy. Int. J. Mol. Sci.,  2018, 19(2), 448.
[http://dx.doi.org/10.3390/ijms19020448] [PMID:  29393886] 
[135] 
Carafa, V.; Altucci, L. Deregulation of cell death in cancer: Recent highlights. Cancers (Basel),  2020, 12(12), 3517-3520.
[http://dx.doi.org/10.3390/cancers12123517] [PMID:  33255936] 
[136] 
Mohamed, M.S.; Bishr, M.K.; Almutairi, F.M.; Ali, A.G. Inhibitors of apoptosis: Clinical implications in cancer. Apoptosis,  2017, 22(12), 1487-1509.
[http://dx.doi.org/10.1007/s10495-017-1429-4] [PMID:  29067538] 
[137] 
Sabt, A.; Abdelhafez, O.M.; El-Haggar, R.S.; Madkour, H.M.F.; Eldehna, W.M.; El-Khrisy, E.E.A.M.; Abdel-Rahman, M.A.; Rashed, L.A. Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: Synthesis, in vitro biological evaluation, and QSAR studies. J. Enzyme Inhib. Med. Chem.,  2018, 33(1), 1095-1107.
[http://dx.doi.org/10.1080/14756366.2018.1477137] [PMID:  29944015] 
[138] 
Mohamed, T.K.; Batran, R.Z.; Elseginy, S.A.; Ali, M.M.; Mahmoud, A.E. Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis. Bioorg. Chem.,  2019, 85, 253-273.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.040] [PMID:  30641320] 
[139] 
Sharma, P.; Srinivasa Reddy, T.; Thummuri, D.; Senwar, K.R.; Praveen Kumar, N.; Naidu, V.G.M.; Bhargava, S.K.; Shankaraiah, N. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents. Eur. J. Med. Chem.,  2016, 124, 608-621.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.029] [PMID:  27614408] 
[140] 
He, H.; Wang, X.; Shi, L.; Yin, W.; Yang, Z.; He, H.; Liang, Y. Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide-hydrazone and carboxamide moiety. Bioorg. Med. Chem. Lett.,  2016, 26(14), 3263-3270.
[http://dx.doi.org/10.1016/j.bmcl.2016.05.059] [PMID:  27262600] 
[141] 
Kumar, P.; Duhan, M.; Kadyan, K.; Bhardwaj, J.K.; Saraf, P.; Mittal, M. Multicomponent synthesis of some molecular hybrid contain-ing thiazole pyrazole as apoptosis inducer. Drug Res. (Stuttg.),  2018, 68(2), 72-79.
[http://dx.doi.org/10.1055/s-0043-116947] [PMID:  28910831] 
[142] 
de Santana, T.I.; Barbosa, M.O.; Gomes, P.A.T.M.; da Cruz, A.C.N.; da Silva, T.G.; Leite, A.C.L. Synthesis, anticancer activity and mechanism of action of new thiazole derivatives. Eur. J. Med. Chem.,  2018, 144, 874-886.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.040] [PMID:  29329071] 
[143] 
Finiuk, N.; Klyuchivska, O.; Ivasechko, I.; Hreniukh, V.; Ostapiuk, Y.; Shalai, Y.; Panchuk, R.; Matiychuk, V.; Obushak, M.; Stoika, R.; Babsky, A. Proapoptotic effects of novel thiazole derivative on human glioma cells. Anticancer Drugs,  2019, 30(1), 27-37.
[http://dx.doi.org/10.1097/CAD.0000000000000686] [PMID:  30130258] 
[144] 
Piechowska, K.; Świtalska, M; Cytarska, J; Jaroch, K; Łuczykowski, K; Chałupka, J; Wietrzyk, J; Misiura, K; Bojko, B; Kruszewski, S; Łączkowski, K.Z Discovery of
 tropinone-thiazole derivatives as potent caspase 3/7 activators, and noncompetitive tyrosinase inhibitors with high antiproliferative activity: Rational design, one-pot tricomponent synthesis, and lipophilicity determination. Eur. J. Med. Chem.,  2019, 175, 162-171.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.006] [PMID:  31082763] 
[145] 
Oliva, P.; Onnis, V.; Balboni, E.; Hamel, E.; Estévez-Sarmiento, F.; Quintana, J.; Estévez, F.; Brancale, A.; Ferla, S.; Manfredini, S.; Romagnoli, R. Synthesis and biological evaluation of 2-substituted benzyl-/phenylethylamino-4-amino-5-aroylthiazoles as apoptosis-inducing anticancer agents. Molecules,  2020, 25(9), 2177.
[http://dx.doi.org/10.3390/molecules25092177] [PMID:  32384805] 
[146] 
Fayed, E.A.; Ammar, Y.A.; Ragab, A.; Gohar, N.A.; Mehany, A.B.M.; Farrag, A.M. In vitro cytotoxic activity of thiazole-indenoquinoxaline hybrids as apoptotic agents, design, synthesis, physicochemical and pharmacokinetic studies. Bioorg. Chem.,  2020, 100, 103951.
[http://dx.doi.org/10.1016/j.bioorg.2020.103951] [PMID:  32450392] 
[147] 
Suma, V.R.; Sreenivasulu, R.; Rao, M.V.B.; Subramanyam, M.; Ahsan, M.J.; Alluri, R.; Rao, K.R.M. Design, synthesis, and biological evaluation of chalcone-linked thiazole-imidazopyridine derivatives as anticancer agents. Med. Chem. Res.,  2020, 29(9), 1643-1654.
[http://dx.doi.org/10.1007/s00044-020-02590-9] 
[148] 
Wang, Y.; Wu, C.; Zhang, Q.; Shan, Y.; Gu, W.; Wang, S. Design, synthesis and biological evaluation of novel β-pinene-based thiazole derivatives as potential anticancer agents via mitochondrial-mediated apoptosis pathway. Bioorg. Chem.,  2019, 84, 468-477.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.010] [PMID:  30576910] 
[149] 
Hegde, M.; Vartak, S.V.; Kavitha, C.V.; Ananda, H.; Prasanna, D.S.; Gopalakrishnan, V.; Choudhary, B.; Rangappa, K.S.; Raghavan, S.C. A benzothiazole derivative (5g) induces DNA damage and potent G2/M arrest in cancer cells. Sci. Rep.,  2017, 7(1), 2533.
[http://dx.doi.org/10.1038/s41598-017-02489-3] [PMID:  28566733] 
[150] 
Liu, D.C.; Gao, M.J.; Huo, Q.; Ma, T.; Wang, Y.; Wu, C.Z. Design, synthesis, and apoptosis-promoting effect evaluation of novel pyra-zole with benzo[d]thiazole derivatives containing aminoguanidine units. J. Enzyme Inhib. Med. Chem.,  2019, 34(1), 829-837.
[http://dx.doi.org/10.1080/14756366.2019.1591391] [PMID:  30915869] 
[151] 
Uremis, N.; Uremis, M.M.; Tolun, F.I.; Ceylan, M.; Doganer, A.; Kurt, A.H. Synthesis of 2-substituted benzothiazole derivatives and their in vitro anticancer effects and antioxidant activities against pancreatic cancer cells. Anticancer Res.,  2017, 37(11), 6381-6389.
[http://dx.doi.org/10.21873/anticanres.12091] [PMID:  29061823] 
[152] 
Philoppes, J.N.; Lamie, P.F. Design and synthesis of new benzoxazole/benzothiazole-phthalimide hybrids as antitumor-apoptotic agents. Bioorg. Chem.,  2019, 89, 102978.
[http://dx.doi.org/10.1016/j.bioorg.2019.102978] [PMID:  31136900] 
[153] 
Shareef, M.A.; Devi, G.P.; Rani Routhu, S.; Kumar, C.G.; Kamal, A.; Babu, B.N. New imidazo[2,1-b]thiazole-based aryl hydrazones: Unravelling their synthesis and antiproliferative and apoptosis-inducing potential. RSC Med. Chem.,  2020, 11(10), 1178-1184.
[http://dx.doi.org/10.1039/D0MD00188K] [PMID:  33479622] 
[154] 
Abdelazeem, A.H.; Alqahtani, A.; Omar, H.A.; Bukhari, S.N.A.; Gouda, A.M. Synthesis, biological evaluation and kinase profiling of novel S-benzo [4, 5] thiazolo [2, 3-c][1, 2, 4] triazole derivatives as cytotoxic agents with apoptosis-inducing activity. J. Mol. Struct.,  2020, 1219, 128567.
[http://dx.doi.org/10.1016/j.molstruc.2020.128567] 
[155] 
Ozgur, A.; Tutar, Y. Heat shock protein 90 inhibitors in oncology. Curr. Proteomics,  2014, 11(1), 2-16.
[http://dx.doi.org/10.2174/1570164611666140415224635] 
[156] 
Biebl, M.M.; Buchner, J. Structure, function, and regulation of the Hsp90 machinery. Cold Spring Harb. Perspect. Biol.,  2019, 11(9), a034017.
[http://dx.doi.org/10.1101/cshperspect.a034017] [PMID:  30745292] 
[157] 
Koca, İ Gümüş M.; Özgür, A.; Dişli, A.; Tutar, Y. A novel approach to inhibit heat shock response as anticancer strategy by couma-rine compounds containing thiazole skeleton. Anticancer. Agents Med. Chem.,  2015, 15(7), 916-930.
[http://dx.doi.org/10.2174/1871520615666150407155623] [PMID:  25846761] 
[158] 
Wing, S.S. Deubiquitinating enzymes in skeletal muscle atrophy-An essential role for USP19. Int. J. Biochem. Cell Biol.,  2016, 79, 462-468.
[http://dx.doi.org/10.1016/j.biocel.2016.07.028] [PMID:  27475983] 
[159] 
Weisberg, E.; Halilovic, E.; Cooke, V.G.; Nonami, A.; Ren, T.; Sanda, T.; Simkin, I.; Yuan, J.; Antonakos, B.; Barys, L.; Ito, M.; Stone, R.; Galinsky, I.; Cowens, K.; Nelson, E.; Sattler, M.; Jeay, S.; Wuerthner, J.U.; McDonough, S.M.; Wiesmann, M.; Griffin, J.D. Inhibi-tion of wild-type p53-expressing AML by the novel small molecule HDM2 inhibitor CGM097. Mol. Cancer Ther.,  2015, 14(10), 2249-2259.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0429] [PMID:  26206331] 
[160] 
Chen, C.; Song, J.; Wang, J.; Xu, C.; Chen, C.; Gu, W.; Sun, H.; Wen, X. Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors. Bioorg. Med. Chem. Lett.,  2017, 27(4), 845-849.
[http://dx.doi.org/10.1016/j.bmcl.2017.01.018] [PMID:  28108249] 
[161] 
Shi, G-X.; Yang, W.S.; Jin, L.; Matter, M.L.; Ramos, J.W. RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases. Proc. Natl. Acad. Sci. USA,  2018, 115(2), E190-E199.
[http://dx.doi.org/10.1073/pnas.1708584115] [PMID:  29279389] 
[162] 
Fascio, M.L.; Errea, M.I.; D’Accorso, N.B. Imidazothiazole and related heterocyclic systems. Synthesis, chemical and biological proper-ties. Eur. J. Med. Chem.,  2015, 90, 666-683.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.012] [PMID:  25499987] 
[163] 
Varga, D.; Crisan, L.; Pacureanu, L. Molecular modeling studies of thiazole derivatives as PIN1 inhibitors. Rev. Roum. Chim.,  2017, 62(4-5), 425-432.https://www.researchgate.net/publication/319479516
[164] 
Zhao, H.; Cui, G.; Jin, J.; Chen, X.; Xu, B. Synthesis and Pin1 inhibitory activity of thiazole derivatives. Bioorg. Med. Chem.,  2016, 24(22), 5911-5920.
[http://dx.doi.org/10.1016/j.bmc.2016.09.049] [PMID:  27692510] 
[165] 
Gehringer, M.; Laufer, S.A. Emerging and re-emerging warheads for targeted covalent inhibitors: Applications in medicinal chemistry and chemical biology. J. Med. Chem.,  2019, 62(12), 5673-5724.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01153] [PMID:  30565923] 
[166] 
Deng, H.; Li, W. Monoacylglycerol lipase inhibitors: Modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders. Acta Pharm. Sin. B,  2020, 10(4), 582-602.
[http://dx.doi.org/10.1016/j.apsb.2019.10.006] [PMID:  32322464] 
[167] 
Wyatt, R.M.; Fraser, I.; Welty, N.; Lord, B.; Wennerholm, M.; Sutton, S.; Ameriks, M.K.; Dugovic, C.; Yun, S.; White, A.; Nguyen, L.; Koudriakova, T.; Tian, G.; Suarez, J.; Szewczuk, L.; Bonnette, W.; Ahn, K.; Ghosh, B.; Flores, C.M.; Connolly, P.J.; Zhu, B.; Macielag, M.J.; Brandt, M.R.; Chevalier, K.; Zhang, S.P.; Lovenberg, T.; Bonaventure, P. Pharmacologic characterization of JNJ-42226314, [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl) piperazin-1-yl]azetidin-1-yl]methanone, a reversible, selective, and potent Mono-acylglycerol Lipase inhibitor. J. Pharmacol. Exp. Ther.,  2020, 372(3), 339-353.
[http://dx.doi.org/10.1124/jpet.119.262139] [PMID:  31818916] 
[168] 
Afzal, O.; Akhtar, M.S.; Kumar, S.; Ali, M.R.; Jaggi, M.; Bawa, S. Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity. Eur. J. Med. Chem.,  2016, 121, 318-330.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.038] [PMID:  27267002] 
[169] 
Supuran, C.T. Structure and function of carbonic anhydrases. Biochem. J.,  2016, 473(14), 2023-2032.
[http://dx.doi.org/10.1042/BCJ20160115] [PMID:  27407171] 
[170] 
Krall, N.; Pretto, F.; Decurtins, W.; Bernardes, G.J.; Supuran, C.T.; Neri, D. A small-molecule drug conjugate for the treatment of car-bonic anhydrase IX expressing tumors. Angew. Chem. Int. Ed. Engl.,  2014, 53(16), 4231-4235.
[http://dx.doi.org/10.1002/anie.201310709] [PMID:  24623670] 
[171] 
Abdoli, M.; Angeli, A.; Bozdag, M.; Carta, F.; Kakanejadifard, A.; Saeidian, H.; Supuran, C.T. Synthesis and carbonic anhydrase I, II, VII, and IX inhibition studies with a series of benzo[d]thiazole-5- and 6-sulfonamides. J. Enzyme Inhib. Med. Chem.,  2017, 32(1), 1071-1078.
[http://dx.doi.org/10.1080/14756366.2017.1356295] [PMID:  28753093] 
[172] 
Turan-Zitouni, G. Altıntop, M.D.; Özdemir, A.; Kaplancıklı Z.A.; Çiftçi, G.A.; Temel, H.E. Synthesis and evaluation of bis-thiazole derivatives as new anticancer agents. Eur. J. Med. Chem.,  2016, 107, 288-294.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.002] [PMID:  26599534] 
[173] 
Gomha, S.M.; Salaheldin, T.A.; Hassaneen, H.M.; Abdel-Aziz, H.M.; Khedr, M.A. Synthesis, characterization and molecular docking of novel bioactive thiazolyl-thiazole derivatives as promising cytotoxic antitumor drug. Molecules,  2015, 21(1), E3.
[http://dx.doi.org/10.3390/molecules21010003] [PMID:  26703554] 
[174] 
Gomha, S.M. El‐Hashash, M.A.; Edrees, M.M.; El‐Arab, E.E. Synthesis, characterization, and molecular docking of novel bis‐thiazolyl thienothiophene derivatives as promising cytotoxic antitumor drug. J. Heterocycl. Chem.,  2017, 54(5), 2686-2695.
[http://dx.doi.org/10.1002/jhet.2869] 
[175] 
Gomha, S.M.; Abdelhamid, A.O.; Abdelrehem, N.A.; Kandeel, S.M. Efficient synthesis of new benzofuran‐based thiazoles and inves-tigation of their cytotoxic activity against human breast carcinoma cell lines. J. Heterocycl. Chem.,  2018, 55(4), 995-1001.
[http://dx.doi.org/10.1002/jhet.3131] 
[176] 
Hosseinzadeh, L.; Aliabadi, A.; Kalantari, M.; Mostafavi, A.; Khajouei, M.R. Synthesis and cytotoxicity evaluation of some new 6-nitro derivatives of thiazole-containing 4-(3H)-quinazolinone. Res. Pharm. Sci.,  2016, 11(3), 210-218.
[PMID: 27499790] 
[177] 
Braga, S.F.P.; Fonseca, N.C.; Ramos, J.P.; Souza-Fagundes, E.M.; Oliveira, R.B. Synthesis and cytotoxicity evaluation of thiosemi-carbazones and their thiazole derivatives. Braz. J. Pharm. Sci.,  2016, 52(2), 299-308.
[http://dx.doi.org/10.1590/S1984-82502016000200008] 
[178] 
Grozav, A.; Porumb, I-D. Găină L.I.; Filip, L.; Hanganu, D. Cytotoxicity and antioxidant potential of novel 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives. Molecules,  2017, 22(2), 260.
[http://dx.doi.org/10.3390/molecules22020260] [PMID:  28208774] 
[179] 
Sridevi, B.; Tangella, Y.; Babu, K.S.; Nanubolu, J.B.; Rani, R.S.; Kumar, C.G.; Meshram, H.; Kamal, A. Sulfamic acid catalyzed one-pot, three-component green approach: Synthesis and cytotoxic evaluation of pyrazolyl-thiazole congeners. New J. Chem.,  2017, 41(10), 3745-3749.
[http://dx.doi.org/10.1039/C7NJ00042A] 
[180] 
Mohareb, R.M.; Abdallah, A.E.M.; Mohamed, A.A. Synthesis of novel thiophene, thiazole and coumarin derivatives based on benzim-idazole nucleus and their cytotoxicity and toxicity evaluations. Chem. Pharm. Bull. (Tokyo),  2018, 66(3), 309-318.
[http://dx.doi.org/10.1248/cpb.c17-00922] [PMID:  29491264] 
[181] 
Shamim, F.; Khan, F.A.; Taha, M.; Khan, K.M. Synthesis and in vitro anti-proliferative capabilities of steroidal thiazole and indole deriv-atives. J. Saudi Chem. Soc.,  2019, 23(7), 775-780.
[http://dx.doi.org/10.1016/j.jscs.2019.05.001] 
[182] 
Sroor, F.M.; Abdelmoniem, A.M.; Abdelhamid, I.A. Facile synthesis, structural activity relationship, molecular modeling and in vitro biological evaluation of new urea derivatives with incorporated isoxazole and thiazole moieties as anticancer agents. ChemistrySelect,  2019, 4(34), 10113-10121.
[http://dx.doi.org/10.1002/slct.201901415] 
[183] 
Abd El-Karim, S.S.; Syam, Y.M.; El Kerdawy, A.M.; Abdelghany, T.M. New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: Synthesis, CDK2 inhibition, QSAR and molecular docking studies. Bioorg. Chem.,  2019, 86, 80-96.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.026] [PMID:  30685646] 
[184] 
Alvarez, N.; Velluti, F.; Guidali, F.; Serra, G.; Kramer, M.G.; Ellena, J.; Facchin, G.; Scarone, L.; Torre, M.H. New BI and TRI-Thiazole copper (II) complexes in the search of new cytotoxic drugs against breast cancer cells. Inorg. Chim. Acta,  2020, 508, 119622.
[http://dx.doi.org/10.1016/j.ica.2020.119622] 
[185] 
Omar, A.M.; Bajorath, J.; Ihmaid, S.; Mohamed, H.M.; El-Agrody, A.M.; Mora, A.; El-Araby, M.E.; Ahmed, H.E.A. Novel molecular discovery of promising amidine-based thiazole analogues as potent dual Matrix Metalloproteinase-2 and 9 inhibitors: Anticancer activity data with prominent cell cycle arrest and DNA fragmentation analysis effects. Bioorg. Chem.,  2020, 101, 103992.
[http://dx.doi.org/10.1016/j.bioorg.2020.103992] [PMID:  32554279] 
[186] 
Sahin, B.; Yaglioglu, A.S.; Ceylan, M. Synthesis and cytotoxic activities of novel 2-(1, 5-bis (aryl) penta-1, 4-dien-2-yl) benzo [d] thia-zol derivatives. Org. Commun.,  2016, 9(3), 65.https://www.acgpubs.org/doc/201808091820118-OC-1602-401.pdf
[187] 
Uremis, M.M. Yağlıoğlu, A.Ş Budak, Y.; Ceylan, M. Synthesis, characterization, in vitro antiproliferative and cytotoxicity effects of a new class of 2-((1R, 2S)-2-((E)-4-substitutedstyryl) cyclooctyl) benzo [d] thiazole derivatives. Org. Commun.,  2017, 10(3), 190-200.
[http://dx.doi.org/10.25135/acg.oc.18.17.02.009] 
[188] 
Mohareb, R.M.; Abdallah, A.E.M.; Ahmed, E.A. Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile. Acta Pharm.,  2017, 67(4), 495-510.
[http://dx.doi.org/10.1515/acph-2017-0040] [PMID:  29337677] 
[189] 
Evren, A.E.; Yurttas, L.; Ekselli, B.; Akalin-Ciftci, G. Synthesis and biological evaluation of 5-methyl-4-phenyl thiazole derivatives as anticancer agents. Phosphorus Sulfur Silicon Relat. Elem.,  2019, 194(8), 820-828.
[http://dx.doi.org/10.1080/10426507.2018.1550642] 
Cite As
Current Medicinal Chemistry

Thiazole and Related Heterocyclic Systems as Anticancer Agents: A Review on Synthetic Strategies, Mechanisms of Action and SAR Studies

Abstract
