Insight into the Synthesis, Biological Activity, and Structure-activity Relationship
of Benzothiazole and Benzothiazole-hydrazone Derivatives:
A Comprehensive Review

Himanshu      Singh; Rajnish      Kumar; Ranjeet   Kumar   Yadav; Avijit      Mazumder; Salahuddin; Bharti      Chauhan; Mohd.   Mustaqeem   Abdullah
Abstract

Heterocyclic compounds constitute the most important part of medicinal as well as organic chemistry. Most of the marketed drugs possess therapeutic activity because of the presence of heterocyclic scaffolds as part of their structure. A slight change in the structure of the heterocyclic moieties may result in a major change in the therapeutic response of the drug candidate. Among all heterocycle compounds, the compounds containing nitrogen and sulfur atoms serve as a unique resource for drug development, such as benzothiazoles. Benzothiazole is a benzofused heterocyclic that is widely reported as a constituent of naturally occurring chemicals and chiefly responsible for their pharmacological potential. It was also reported that the pharmacological activity of BTA may also be influenced by its coupling with aldehydes, ketones, or hydrazines to form respected benzothiazole-hydrazone derivatives. The present comprehensive review consists of various synthesis methods, biological activities, and structure-activity relationships of and targets of benzothiazole and benzothiazole-hydrazone derivatives to provide a wide range of information to medicinal chemists for future research work.
Keywords: Benzothiazole, benzothiazole-hydrazones, patents, marketed products, synthetic approaches, biological activity, structure-activity relationship.
Graphical Abstract

[1]
Kale, T.V.; Burghate, A.S.; Wadhal, S.A. Synthesis and antibacterial activity of n-heterocyclic substituted hydrazone Schiff’s bases. Indo Am. J. Pharm. Res.,  2016, 6, 6404-6410.

[2]
Sharma, P. C.; Sinhmar, A.; Sharma, A.; Rajak, H.; Sharma, P. C.; Sinhmar, A.; Sharma, A.; Rajak, H. Medicinal significance of benzothiazole scaffold: An insight view. J. Enzyme, Inhib. Med. Chem.,  2013, 28(2), 240-266.

[3]
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]

[4]
Irfan, A.; Batool, F.; Zahra Naqvi, S.A.; Islam, A.; Osman, S.M.; Nocentini, A.; Alissa, S.A.; Supuran, C.T. Benzothiazole derivatives as anticancer agents. J. Enzyme Inhib. Med. Chem.,  2020, 35(1), 265-279.
 [http://dx.doi.org/10.1080/14756366.2019.1698036] [PMID: 31790602]

[5]
Jaiswal, S.; Mishra, P.A. The different kinds of reaction involved in synthesis of 2-substituted 2enzothiazole and its derivatives: A review. J. Pharm. Biol. Chem. Sci.,  2012, 3, 631-641.

[6]
Studies, C. Riluzole for amyotrophic lateral sclerosis. Drug Ther. Bull.,  1997, 35(2), 11-12.
 [http://dx.doi.org/10.1136/dtb.1997.35211] [PMID: 9282413]

[7]
Sebastiao, M.; Quittot, N.; Bourgault, S.; Thioflavin, T. Thioflavin T fluorescence to analyse amyloid formation kinetics: Measurement frequency as a factor explaining irreproducibility. Anal. Biochem.,  2017, 532, 83-86.
 [http://dx.doi.org/10.1016/j.ab.2017.06.007] [PMID: 28623075]

[8]
Hubble, J.P.; Koller, W.C.; Cutler, N.R.; Sramek, J.J.; Friedman, J.; Goetz, C.; Ranhosky, A.; Korts, D.; Elvin, A. Pramipexole in patients with early Parkinson’s disease. Clin. Neuropharmacol.,  1995, 18(4), 338-347.
 [http://dx.doi.org/10.1097/00002826-199508000-00006] [PMID: 8665547]

[9]
Winkelman, J.W.; Sethi, K.D.; Kushida, C.A.; Becker, P.M.; Koester, J.; Cappola, J.J.; Reess, J. Efficacy and safety of pramipexole in restless legs syndrome. Neurology,  2006, 67(6), 1034-1039.
 [http://dx.doi.org/10.1212/01.wnl.0000231513.23919.a1] [PMID: 16931507]

[10]
Mocharla, V.P.; Colasson, B.; Lee, L.V.; Röper, S.; Sharpless, K.B.; Wong, C.; Kolb, H.C. In situ click chemistry: Enzyme-generated inhibitors of carbonic anhydrase II. Enzyme Inhib.,  2005, 117, 118-122.

[11]
Scheetz ME, I.I.; Schinitsky, M.R.; Carlson, D.G.; Schinitsky, M.R. 
Frentizole, a novel immunosuppressive, and azathioprine: Their comparative effects on host resistance to Pseudomonas aeruginosa, Candida albicans, herpes simplex virus, and influenza (Ann Arbor) virus. Infect. Immun.,  1977, 15(1), 145-148. [http://dx.doi.org/10.1128/iai.15.1.145-148.1977] [PMID: 188761]
[12]
Wu, Z.; Wang, G.; Zhang, B.; Dai, T.; Gu, A.; Li, X.; Cheng, X.; Liu, P.; Hao, J.; Liu, X. Metabolic mechanism of plant defense against rice blast induced by probenazole. Metabolites,  2021, 11(4), 246.
 [http://dx.doi.org/10.3390/metabo11040246] [PMID: 33923492]

[13]
Laursen, L.C.; Lindqvist, A.; Hepburn, T.; Lloyd, J.; Perrett, J.; Sanders, N.; Rocchiccioli, K. The role of the novel D2/beta2-agonist, Viozan (sibenadet HCl), in the treatment of symptoms of chronic obstructive pulmonary disease: Results of a large-scale clinical investigation. Respir. Med.,  2003, 97(Suppl. A), S23-S33.
 [http://dx.doi.org/10.1016/S0954-6111(03)80012-4] [PMID: 12564608]

[14]
Abrol, S.; Bodla, R.B.; Goswami, C. A comprehensive review on benzothiazole derivatives for their biological activities. Int. J. Pharm. Sci. Res.,  2019, 10(7), 3196-3209.

[15]
Tariq, S.; Kamboj, P.; Amir, M. Therapeutic advancement of benzothiazole derivatives in the last decennial period. Arch. Pharm. (Weinheim),  2019, 352(1), e1800170.
 [PMID: 30488989]

[16]
Johnson, B.K.; Colvin, C.J.; Needle, D.B.; Medie, F.; Champion, P.A.D.G.; Abramovitch, R.B. The carbonic anhydrase inhibitor ethoxzolamide inhibits the Mycobacterium tuberculosis PhoPR regulon and esx-1 secretion and attenuates virulence. Antimicrob. Agents Chemother.,  2015, 59(8), 4436-4445.
 [http://dx.doi.org/10.1128/AAC.00719-15]

[17]
Ghonim, A.E.; Ligresti, A.; Rabbito, A.; Mokhtar, A.; Di, V.; Osman, N.A.; Abadi, A.H. Structure-activity relationships of thiazole and benzothiazole derivatives as selective cannabinoid CB2 agonists with in vivo anti- inflammatory properties. Eur. J. Med. Chem.,  2019, 180, 154-170.
 [http://dx.doi.org/10.1016/j.ejmech.2019.07.002] [PMID: 31302448]

[18]
Liu, Y.; Wang, Y.; Dong, G.; Zhang, Y.; Wu, S.; Miao, Z.; Yao, J.; Zhang, W.; Sheng, C. Novel benzothiazole derivatives with a broad antifungal spectrum: Design, synthesis and structure-activity relationships. MedChemComm,  2013, 4(12), 1551-1561.
 [http://dx.doi.org/10.1039/c3md00215b]

[19]
Catalano, A.; Carocci, A.; Defrenza, I.; Muraglia, M.; Carrieri, A.; Van Bambeke, F.; Rosato, A.; Corbo, F.; Franchini, C. 2-Aminobenzothiazole derivatives: Search for new antifungal agents. Eur. J. Med. Chem.,  2013, 64, 357-364.
 [http://dx.doi.org/10.1016/j.ejmech.2013.03.064] [PMID: 23644218]

[20]
Zhao, S.; Zhao, L.; Zhang, X.; Liu, C.; Hao, C.; Xie, H.; Sun, B.; Zhao, D.; Cheng, M. Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents. Eur. J. Med. Chem.,  2016, 123, 514-522.
 [http://dx.doi.org/10.1016/j.ejmech.2016.07.067] [PMID: 27494168]

[21]
Meltzer-Mats, E.; Babai-Shani, G.; Pasternak, L.; Uritsky, N.; Getter, T.; Viskind, O.; Eckel, J.; Cerasi, E.; Senderowitz, H.; Sasson, S.; Gruzman, A. Synthesis and mechanism of hypoglycemic activity of benzothiazole derivatives. J. Med. Chem.,  2013, 56(13), 5335-5350.
 [http://dx.doi.org/10.1021/jm4001488] [PMID: 23750537]

[22]
Cai, J.; Sun, M.; Wu, X.; Chen, J.; Wang, P.; Zong, X.; Ji, M. Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents. Eur. J. Med. Chem.,  2013, 63, 702-712.
 [http://dx.doi.org/10.1016/j.ejmech.2013.03.013] [PMID: 23567960]

[23]
Shi, X.H.; Wang, Z.; Xia, Y.; Ye, T.H.; Deng, M.; Xu, Y.Z.; Wei, Y.Q.; Yu, L.T. Synthesis and biological evaluation of novel benzothiazole-2-thiol derivatives as potential anticancer agents. Molecules,  2012, 17(4), 3933-3944.
 [http://dx.doi.org/10.3390/molecules17043933] [PMID: 22466853]

[24]
Chhabra, M.; Sinha, S.; Banerjee, S.; Paira, P. An efficient green synthesis of 2-arylbenzothiazole analogues as potent antibacterial and anticancer agents. Bioorg. Med. Chem. Lett.,  2016, 26(1), 213-217.
 [PMID: 26590102]

[25]
Er, M.; Özer, A.; Direkel, Ş.; Karakurt, T.; Tahtaci, H. Novel substituted benzothiazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives: Synthesis, characterization, molecular docking study, and investigation of their in vitro antileishmanial and antibacterial activities. J. Mol. Struct.,  2019, 1194, 284-296.
 [http://dx.doi.org/10.1016/j.molstruc.2019.05.104]

[26]
Munirajasekhar, D.; Hamja, M.; Mali, S.V. Synthesis and anthelmintic activity of 2-amino-6-substituted benzothiazoles. Int. Res. J. Harm.,  2011, 2(1), 114-117.

[27]
Sharma, P.C.; Kumar, R.; Chaudhary, M.; Sharma, A.; Rajak, H. Synthesis and biological evaluation of novel benzothiazole clubbed fluoroquinolone derivatives. J. Enzyme Inhib. Med. Chem.,  2013, 28(1), 1-10.
 [http://dx.doi.org/10.3109/14756366.2011.611943] [PMID: 21981002]

[28]
Rajareddy, A.; Murthy, M.S. Synthesis, characterization, and anthelmintic activity of novel benzothiazole derivatives containing indole moieties. Asian J. Pharm. Clin. Res.,  2019, 12(3), 321-325.
 [http://dx.doi.org/10.22159/ajpcr.2019.v12i3.30530]

[29]
Base, S.; Bs, S.; Jayachandran, E.; Va, J.; Gm, S. Anthelmintic activity of newly synthesized moities of fluoro benzothiazole. Res. J. Pharm. Biol. Chem. Sci.,  2014, 2(1), 510-515.

[30]
Kumar, G.; Singh, N.P. Synthesis, anti-inflammatory and analgesic evaluation of thiazole/oxazole substituted benzothiazole derivatives. Bioorg. Chem.,  2021, 107, 104608.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104608] [PMID: 33465668]

[31]
Nath, R.; Shahar Yar, M.; Pathania, S.; Grover, G.; Debnath, B.; Akhtar, M.J. Synthesis and anticonvulsant evaluation of indoline derivatives of functionalized aryloxadiazole amine and benzothiazole acetamide. J. Mol. Struct.,  2021, 1228, 129742.
 [http://dx.doi.org/10.1016/j.molstruc.2020.129742]

[32]
Padalkar, V.S.; Gupta, V.D.; Phatangare, K.R.; Patil, V.S.; Umape, P.G.; Sekar, N. Synthesis of novel dipodal-benzimidazole, benzoxazole and benzothiazole from cyanuric chloride: Structural, photophysical and antimicrobial studies. J. Saudi Chem. Soc.,  2014, 18(3), 262-268.
 [http://dx.doi.org/10.1016/j.jscs.2011.07.001]

[33]
Srivastava, A.; Mishra, A.P.; Chandra, S.; Bajpai, A. Benzothiazole derivative: A review on its pharmacological importance towards synthesis of lead. Int. J. Pharm. Sci. Res.,  2019, 10(4), 1553-1566.

[34]
Hu, Y.; MacMillan, J.B. Erythrazoles A À B, cytotoxic benzothiazoles from a marine-derived. Org. Lett.,  2011, 13(24), 6580-6583.
 [http://dx.doi.org/10.1021/ol202944g] [PMID: 22106936]

[35]
Chill, L.; Rudi, A.; Benayahu, Y.; Kashman, Y. Violatinctamine, a new heterocyclic compound from the marine tunicate Cystodytes cf. violatinctus. Tetrahedron Lett.,  2004, 45(42), 7925-7928.
 [http://dx.doi.org/10.1016/j.tetlet.2004.08.137]

[36]
Scheuer, A.R.C. Pentacyclic alkaloids from a tunicate and its prosobranch mollusk predator Chelynotus semperi. Am. Chem. Soc.,  1989, 4426-4431.

[37]
Gunawardana, G.P.; Kohmoto, S.; Gunasekera, S.P.; McConnell, O.J.; Koehn, F.E. Dercitin, a new biologically active acridine alkaloid from a deep water marine sponge, dercitus SP. J. Am. Chem. Soc.,  1988, 110(14), 4856-4858.
 [http://dx.doi.org/10.1021/ja00222a071]

[38]
Asif, M.; Husain, A. Analgesic, anti-inflammatory, and antiplatelet profile of hydrazones containing synthetic molecules. J. Appl. Chem.,  2013, 2013, 1-7.
 [http://dx.doi.org/10.1155/2013/247203]

[39]
Abdel-Wahab, B.F.; Awad, G.E.A.; Badria, F.A. Synthesis, antimicrobial, antioxidant, anti-hemolytic and cytotoxic evaluation of new imidazole-based heterocycles. Eur. J. Med. Chem.,  2011, 46(5), 1505-1511.
 [http://dx.doi.org/10.1016/j.ejmech.2011.01.062] [PMID: 21353349]

[40]
Kumar, N.; Chauhan, L.S.; Dashora, N.; Sharma, C.S. Review article anticonvulant potential of hydrazone derivatives: A review. Sch. Acad. J. Pharm.,  2014, 3(5), 366-373.

[41]
Lindgren, E.B.; de Brito, M.A.; Vasconcelos, T.R.A.; de Moraes, M.O.; Montenegro, R.C.; Yoneda, J.D.; Leal, K.Z. Synthesis and anticancer activity of (E)-2-benzothiazole hydrazones. Eur. J. Med. Chem.,  2014, 86, 12-16.
 [http://dx.doi.org/10.1016/j.ejmech.2014.08.039] [PMID: 25147145]

[42]
Edrees, M.M.; Farghaly, T.A.; El-Hag, F.A.A.; Abdalla, M.M. Antimicrobial, antitumor and 5α-reductase inhibitor activities of some hydrazonoyl substituted pyrimidinones. Eur. J. Med. Chem.,  2010, 45(12), 5702-5707.
 [http://dx.doi.org/10.1016/j.ejmech.2010.09.026] [PMID: 20933305]

[43]
Kolate, S.S.; Waghulde, G.P.; Patil, C.J.; Synthesis, C.S. Spectroscopic characterization and biological evaluation of some 6-nitro-benzothiazole-2-yl-hydrazone derivatives. J. Pharm. Chem. Biol. Sci.,  2018, 6(3), 143-150.

[44]
Tripathi, L.; Singh, R.; Stables, J.P. Design  synthesis of N′-[substituted] pyridine-4-carbohydrazides as potential anticonvulsant agents. Eur. J. Med. Chem.,  2011, 46(2), 509-518.
 [http://dx.doi.org/10.1016/j.ejmech.2010.11.030] [PMID: 21167624]

[45]
Asati, V.; Sahu, N.K.; Rathore, A.; Sahu, S.; Kohli, D.V. Synthesis, characterization and antimicrobial evaluation of some 1,3-benzothiazole-2-yl-hydrazone derivatives. Arab. J. Chem.,  2015, 8(4), 495-499.
 [http://dx.doi.org/10.1016/j.arabjc.2011.01.036]

[46]
Klunk, W.E.; Mathis, C.A.; Wang, Y. Benzothiazole derivative compounds, composition and uses. U.S. Patent 20130004422, January 3, 2013.

[47]
Dahl, R.; Lee, A.Y.; Kho, C.; Hajjar, R.J. Benzothiazole or benzoxazole compounds as sumo activators. W.O. Patent 2014036242, March 6, 2014.

[48]
Klunk, W.E.; Mathis, C.A.; Wang, Y. Benzothiazole derivative compounds, composition and uses. U.S. Patent 8691185, April 8, 2014.

[49]
Surivet, J.P.; Chapoux, G.; Mirre, A. Antibacterial benzothiazole derivatives. W.O. Patent 2016079688, May 26, 2016.

[50]
Abert, E.; Bacque, E.; Nemecek, C.; Ugolini, A.; Wentzle, S. 6-triazolopyridine sulfanyl benzpthiazole derivatives as MET inhibitors. U.S. Patent 9321777, April 26, 2016.

[51]
Chauhan, K.; Kumari, B. Novel benzothiazole derivatives with enhanced biological activity. U.S. Patent 2017025980, February 16, 2017.

[52]
Thede, K.; Zorn, L.; Steigemann, P.; Grunewald, S.; Sperl, C.; Neuhaus, R.; Schwede, W.; Christian, S.; Gunthier, J. Substituted 2-(1H-pyrazol-1-yl)-benzothiazole compounds. W.O. Patent 2017063966, April 20, 2017.

[53]
Terranova, Z.L. Benzothiazole amphiphiles. W.O. Patent 120198, July 13, 2017.

[54]
Almstead, J.K.; Izzo, N.J.; Jones, D.R.; Kawamoto, R.M. Medicinal uses of hydrazones. U.S. Patent 20040053977, March 1, 2004.

[55]
Cuenoud, B.; Fairhurst, R.A.; Taylor, R.J.; Beattie, D. Benzothiazole derivatives having beta-2-adrenoreceptor agonist activity. W.O. Patent 2004016601, February 26, 2004.

[56]
Hofmann, J.; Heinisch, G.; Easmon, J.; Purstinger, G.; Fiebig, H.H. Heterocyclic hydrazones as novel anti-cancer agents. C.A. Patent 2413971, November 02, 2010.

[57]
Schumacher, R.; Ma, J.; Danca, M.D.; Xie, W.; Nguyen, T.M.; Tehim, A. 1H-Indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof. U.S. Patent 20070135417, June 14, 2007.

[58]
Watson, K.G.; Lessene, G.L.; Baell, J.B.; Huang, D.C.S.; Street, I.P.; Adams, J.M.; Colman, P.M.; Sleebs, B.E.; Smith, B.J.; Czabotar, P.E. Benzothiazole compounds. U.S. Patent 20100197711, August 5, 2010.

[59]
Kamal, A.; Shetti, R.; Swapna, P.; Azeeza, S.; Reddy, A.M.; Khan, I.A.; Abdullah, T.S.; Sharma, S.; Kalia, N.P. Synthesis of new benzothiazole derivatives as potential anti-tubercular agents U.S. Patent 20160175303, June 23, 2016.

[60]
Xing, Q.; Ma, Y.; Xie, H.; Xiao, F.; Zhang, F.; Deng, G.J. Iron-promoted three-component 2-substituted benzothiazole formation via nitroarene ortho-C-H sulfuration with elemental sulfur. J. Org. Chem.,  2019, 84(3), 1238-1246.
 [http://dx.doi.org/10.1021/acs.joc.8b02619] [PMID: 30606012]

[61]
Sun, Y.; Jiang, H.; Wu, W.; Zeng, W.; Wu, X. Copper-Catalyzed Synthesis of Substituted Benzothiazoles via Condensation of 2-Aminobenzenethiols with Nitriles. 2013, 20, 2-5.

[62]
Bastug, G.; Eviolitte, C.; Markó, I.E. Functionalized orthoesters as powerful building blocks for the efficient preparation of heteroaromatic bicycles. Org. Lett.,  2012, 14(13), 3502-3505.
 [http://dx.doi.org/10.1021/ol301472a] [PMID: 22735031]

[63]
Husain, A.; Madhesia, D.; Rashid, M.; Ahmad, A.; Khan, S.A. Synthesis and in vivo diuretic activity of some new benzothiazole sulfonamides containing quinoxaline ring system. J. Enzyme Inhib. Med. Chem.,  2016, 31(6), 1682-1689.
 [http://dx.doi.org/10.3109/14756366.2015.1128425] [PMID: 26739592]

[64]
Hua, R.; Lia, X.; Tonga, Y.; Miaoa, D.; Pana, Q.; Jianga, Z.; Gana, H.; Han, S. Catalyst-free synthesis of 2-arylbenzothiazoles in an air/DMSO oxidant system. Synlett.,  2016, 27. [A-D.].

[65]
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]

[66]
Dey, A.; Hajra, A. Metal-free synthesis of 2-arylbenzothiazoles from aldehydes, amines, and thiocyanate. Org. Lett.,  2019, 21(6), 1686-1689.
 [http://dx.doi.org/10.1021/acs.orglett.9b00245] [PMID: 30811211]

[67]
Gao, M.Y.; Li, J.H.; Zhang, S.B.; Chen, L.J.; Li, Y.S.; Dong, Z.B. A mild synthesis of 2-substituted benzothiazoles via nickel-catalyzed intramolecular oxidative C-H functionalization. J. Org. Chem.,  2020, 85(2), 493-500.
 [http://dx.doi.org/10.1021/acs.joc.9b02543] [PMID: 31845809]

[68]
Wang, X.; Li, X.; Hu, R.; Yang, Z.; Gu, R.; Ding, S.; Li, P.; Han, S. Elemental sulfur-mediated decarboxylative redox cyclization reaction: Copper-catalyzed synthesis of 2-substituted benzothiazoles. Synlett.,  2018, 29(2), 219-224.
 [http://dx.doi.org/10.1055/s-0036-1589112]

[69]
Xu, W.; Zeng, M.T.; Liu, M.; Liu, S.S.; Li, Y.S.; Dong, Z.B. Palladium-catalyzed synthesis of 2-aminobenzothiazoles through tandem reaction. Synth.,  2017, 49(14), 3084-3090.
 [http://dx.doi.org/10.1055/s-0036-1588835]

[70]
Huang, Y.; Zhou, P.; Wu, W.; Jiang, H. Selective construction of 2-substituted benzothiazoles from o-iodoaniline derivatives S8 and N-tosylhydrazones. J. Org. Chem.,  2018, 83(4), 2460-2466.
 [http://dx.doi.org/10.1021/acs.joc.7b03118] [PMID: 29337553]

[71]
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]

[72]
Anh, H.; Le, N.; Hoang, L.; Nhu, Q.; Nguyen, B. Straightforward synthesis of benzoxazoles and benzothiazoles via photocatalytic radical cyclization of 2-substituted anilines with aldehydes. Catal. Commun.,  2020, 145(June), 106120.

[73]
Duangkamol, C.; Phakhodee, W.; Phakhodee, W.; Pattarawarapan, M.; Pattarawarapan, M. Potassium periodate mediated oxidative cyclodesulfurization toward benzofused nitrogen heterocycles. Synth.,  2020, 52(13), 1981-1990.
 [http://dx.doi.org/10.1055/s-0039-1690855]

[74]
Liu, J.; Gui, Q.; Yang, Z.; Tan, Z.; Guo, R.; Shi, J.C. Synthesis of 2-substituted benzothiazoles from 1-iodo-2-nitrobenzenes by a copper-catalyzed one-pot three-component reaction. Synth.,  2013, 45(7), 943-951.
 [http://dx.doi.org/10.1055/s-0032-1318304]

[75]
Zhang, X.; Zeng, W.; Yang, Y.; Huang, H.; Liang, Y. Copper-catalyzed double C-S bonds formation via different paths: Synthesis of benzothiazoles from N-benzyl-2-iodoaniline and potassium sulfide. Org. Lett.,  2014, 16(3), 876-879.
 [http://dx.doi.org/10.1021/ol403638d] [PMID: 24467655]

[76]
Zhao, J.; Huang, H.; Wu, W.; Chen, H.; Jiang, H. Metal-free synthesis of 2-aminobenzothiazoles via aerobic oxidative cyclization/dehydrogenation of cyclohexanones and thioureas. Org. Lett.,  2013, 15(11), 2604-2607.
 [http://dx.doi.org/10.1021/ol400773k] [PMID: 23662734]

[77]
Wang, J.; Zong, Y.; Zhang, X.; Gao, Y.; Li, Z.; Yue, G.; Quan, Z.; Wang, X. Synthesis of N-benzothiazol-2-yl-amides by an iron-catalyzed oxidative C(Sp2)-H functionalization. Synlett.,  2014, 25(15), 2143-2148.
 [http://dx.doi.org/10.1055/s-0034-1378547]

[78]
Kumar, K. R.; Satyanarayana, P. V. V.; Srinivasa Reddy, B. NaHSO4 - SiO2 -promoted solvent-free synthesis of benzoxazoles, benzimidazoles, and benzothiazole derivatives. J. Chem.,  2013, 2013.

[79]
Kim, J.; Oh, K. Copper-catalyzed aerobic oxidation of amines to benzothiazoles via cross coupling of amines and arene thiolation sequence. Adv. Synth. Catal.,  2020, 362(17), 3576-3582.
 [http://dx.doi.org/10.1002/adsc.202000598]

[80]
Nguyen, T.B.; Pasturaud, K.; Ermolenko, L.; Al-Mourabit, A. Concise access to 2-aroylbenzothiazoles by redox condensation reaction between o-halonitrobenzenes, acetophenones, and elemental sulfur. Org. Lett.,  2015, 17(10), 2562-2565.
 [http://dx.doi.org/10.1021/acs.orglett.5b01182] [PMID: 25929738]

[81]
Xu, Y.; Li, B.; Zhang, X.; Fan, X. Metal-free synthesis of 2-aminobenzothiazoles via iodine-catalyzed and oxygen-promoted cascade reactions of isothiocyanatobenzenes with amines. J. Org. Chem.,  2017, 82(18), 9637-9646.
 [http://dx.doi.org/10.1021/acs.joc.7b01683] [PMID: 28812346]

[82]
Luo, K.; Yang, W.C.; Wei, K.; Liu, Y.; Wang, J.K.; Wu, L. di-tert-butyl peroxide-mediated radical C(sp2/sp3)-S bond cleavage and group-transfer cyclization. Org. Lett.,  2019, 21(19), 7851-7856.
 [http://dx.doi.org/10.1021/acs.orglett.9b02837] [PMID: 31524412]

[83]
Zhang, J.; Zhao, X.; Liu, P.; Sun, P. TBHP/KI-promoted annulation of anilines, ethers, and elemental sulfur: Access to 2-aryl-, 2-heteroaryl-, or 2-alkyl-substituted benzothiazoles. J. Org. Chem.,  2019, 84(19), 12596-12605.
 [http://dx.doi.org/10.1021/acs.joc.9b02145] [PMID: 31502839]

[84]
Gorepatil, P.B.; Mane, Y.D.; Ingle, V.S. Samarium (III) triflate as an efficient and reusable catalyst for facile synthesis of benzoxazoles and benzothiazoles in aqueous medium letter. Synlett.,  2013, 24(17), 2241-2244.

[85]
Zhu, Y.P.; Jia, F.C.; Liu, M.C.; Wu, A.X. A multipathway coupled domino strategy: Metal-free oxidative cyclization for one-pot synthesis of 2-acylbenzothiazoles from multiform substrates. Org. Lett.,  2012, 14(17), 4414-4417.
 [http://dx.doi.org/10.1021/ol301921t] [PMID: 22924707]

[86]
Choudhary, S.; Kini, S.G.; Mubeen, M. Antioxidant activity of novel coumarin substituted benzothiazole derivatives. Der Pharma Chem.,  2013, 5(4), 213-222.

[87]
Verma, A.K.; Martin, A.; Singh, A.K. Synthesis, characterization and evaluation of anti-inflammatory and analgesic activity of benzothiazole derivatives. Indian J. Pharm. Biol. Res.,  2014, 2(03), 84-89.
 [http://dx.doi.org/10.30750/ijpbr.2.3.14]

[88]
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]

[89]
Bala, R.; Kumari, P.; Sood, S.; Kumar, V.; Singh, N.; Singh, K. Phthaloyl dichloride–DMF mediated synthesis of benzothiazole-based 4-formylpyrazole derivatives: Studies on their antimicrobial and antioxidant activities. J. Heterocycl. Chem.,  2018, 55(11), 2507-2515.
 [http://dx.doi.org/10.1002/jhet.3282]

[90]
Zheng, X.J.; Li, C.S.; Cui, M.Y.; Song, Z.W.; Bai, X.Q.; Liang, C.W.; Wang, H.Y.; Zhang, T.Y. Synthesis, biological evaluation of benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety as potential anti-oxidant and anti-inflammatory agents. Bioorg. Med. Chem. Lett.,  2020, 30(13), 127237.
 [http://dx.doi.org/10.1016/j.bmcl.2020.127237] [PMID: 32386981]

[91]
Mor, S.; Sindhu, S.; Khatri, M.; Singh, N.; Vasudeva, N.; Panihar, N. Synthesis, type II diabetes inhibitory activity, and antimicrobial tests of benzothiazole derivatives bridged with indenedione by methylenehydrazone. Russ. J. Gen. Chem.,  2019, 89(9), 1867-1873.
 [http://dx.doi.org/10.1134/S1070363219090226]

[92]
Al-Sultani, Kh.T.A.; Al-Lami, N. Antimicrobial Activity of new synthesized aza -beta lactam and tetrazole derivatives bearing imidazo[2,1-b]benzothiazole moiety. Egypt. J. Chem.,  2021, 64(6), 2953-2961.
 [http://dx.doi.org/10.21608/ejchem.2021.55736.3175]

[93]
Weng, J.Q.; Tan, C.X.; Liu, X.H. Synthesis and fungicidal activity of hydrazones containing 4-methylbenzo[d]thiazole moiety. J. Pestic. Sci.,  2012, 37(2), 164-168.
 [http://dx.doi.org/10.1584/jpestics.G11-41]

[94]
Taha, M.; Arbin, M.; Ahmat, N.; Imran, S.; Rahim, F. Bioorganic chemistry synthesis: Small library of hybrid scaffolds of benzothiazole having hydrazone and evaluation of their b -glucuronidase activity. Bioorg. Chem.,  2018, 77, 47-55.
 [http://dx.doi.org/10.1016/j.bioorg.2018.01.002] [PMID: 29331764]

[95]
Mokhtar, A.M.; El-Messery, S.M.; Ghaly, M.A.; Hassan, G.S. Targeting EGFR tyrosine kinase: Synthesis, in vitro antitumor evaluation, and molecular modeling studies of benzothiazole-based derivatives. Bioorg. Chem.,  2020, 104, 104259.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104259] [PMID: 32919134]

[96]
Sultana, F.; Saifi, M.A.; Syed, R.; Mani, G.S.; Shaik, S.P.; Osas, E.G.S.; Godugu, C.; Shahjahan, S.; Kamal, A. Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents. New J. Chem.,  2019, 43(18), 7150-7161.
 [http://dx.doi.org/10.1039/C8NJ06517A]

[97]
Yurttaş, L.; Kaplancıklı, Z.A.; Göger, G.; Demirci, F. Synthesis and anticandidal evaluation of new benzothiazole derivatives with hydrazone moiety. J. Enzyme Inhib. Med. Chem.,  2016, 31(5), 714-720.
 [http://dx.doi.org/10.3109/14756366.2015.1060481] [PMID: 26247354]

[98]
Ilgın, S.; Osmaniye, D.; Levent, S.; Sa glık, B. m. N.; Evik, U. A.; Avuşo glu, B. l. K.; Zkay, Y.; Kaplancıklı, Z. A. Design and synthesis of new benzothiazole compounds as selective HMAO-B inhibitors. Molecules,  2017, 22(12)
 [http://dx.doi.org/10.3390/molecules22122187] [PMID: 29232838]

[99]
Aruna, G.; Kulkarni, R.; Machaa, B.; Jojula, M.; Gunda, S.; Achaiah, G. Design, synthesis and evaluation of aryloxybenzylidene hydrazinyl-benzoxazoles/benzothiazoles analogs as antimycobacterial agents. Asian J. Org. Med. Chem.,  2020, 5(3), 185-191.

[100]
Osmaniye, D.; Levent, S.; Karaduman, A.B.; Ilgın, S.; Özkay, Y.; Kaplancıklı, Z.A. Synthesis of new benzothiazole acylhydrazones as anticancer agents. Molecules,  2018, 23(5), 1-14.
 [http://dx.doi.org/10.3390/molecules23051054] [PMID: 29724002]

[101]
Tripathi, R. K. P.; Ayyannan, S. R. Synthesis, characterization and antimicrobial evaluation of some new benzothiazole derivatives. Int. J. Pharm. Pharm. Sci.,  2016, 7(10), 2-5.

[102]
Sarkar, S.; Siddiqui, A.A.; Saha, S.J.; De, R.; Mazumder, S.; Banerjee, C.; Iqbal, M.S.; Nag, S.; Adhikari, S.; Bandyopadhyay, U. Antimalarial activity of small-molecule benzothiazole hydrazones. Antimicrob. Agents Chemother.,  2016, 60(7), 4217-4228.
 [http://dx.doi.org/10.1128/AAC.01575-15] [PMID: 27139466]

[103]
Chauhan, D.; Siddiqui, A.A.; Kataria, R.; Singh, R. Synthesis, characterization and antimicrobial evaluation of some new benzothiazole derivatives. Int. J. Pharm. Pharm. Sci.,  2015, 7(10), 2-5.

[104]
Singh, V.; Sharma, P.; Yadav, A.; Muttu, C.T.; Ranjeeta, V. Microwave assisted synthesis of fluoro, chloro, 2-N(substituted Schiffs bases) amino benzothiazoles as potential antimicrobial and antitubercular agents. Pharm. Res.,  2009, 192-198.

[105]
Dkhar, L.; Banothu, V.; Kaminsky, W.; Kollipara, M.R. Synthesis of half sandwich platinum group metal complexes containing pyridyl benzothiazole hydrazones: Study of bonding modes and antimicrobial activity. J. Organomet. Chem.,  2020, 914, 121225.
 [http://dx.doi.org/10.1016/j.jorganchem.2020.121225]

[106]
Ugwu, D.I.; Okoro, U.C.; Ukoha, P.O.; Gupta, A.; Okafor, S.N. Novel anti-inflammatory and analgesic agents: Synthesis, molecular docking and in vivo studies. J. Enzyme Inhib. Med. Chem.,  2018, 33(1), 405-415.
 [http://dx.doi.org/10.1080/14756366.2018.1426573] [PMID: 29372659]

[107]
Sadhasivam, G.; Kulanthai, K. Synthesis, characterization, and evaluation of anti-inflammatory and anti-diabetic activity of new benzothiazole derivatives. J. Chem. Pharm. Res.,  2015, 7(8), 425-431.

[108]
Patil, V.; Asrondkar, A.; Bhadane, V.; Bobade, A.S. Synthesis and anti-inflammatory activity of 2-amino-6-methoxy benzothiazole derivative. J. Appl. Chem.,  2015, 8(1), 1-2.

[109]
Racané, L.; Ptiček, L.; Fajdetić, G.; Tralić-Kulenović, V.; Klobučar, M.; Kraljević Pavelić, S.; Perić, M.; Paljetak, H.C.; Verbanac, D.; Starčević, K. Green synthesis and biological evaluation of 6-substituted-2-(2-hydroxy/methoxy phenyl)benzothiazole derivatives as potential antioxidant, antibacterial and antitumor agents. Bioorg. Chem.,  2020, 95(95), 103537.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103537] [PMID: 31884142]

[110]
Mariappan, G.; Prabhat, P.; Sutharson, L.; Banerjee, J.; Patangia, U.N. S. Synthesis and antidiabetic evaluation of benzothiazole derivatives. J. Korean Chem. Soc.,  2012, 56(2), 251-256.
 [http://dx.doi.org/10.5012/jkcs.2012.56.2.251]

[111]
Puranik, N.V.; Puntambekar, H.M.; Srivastava, P. Antidiabetic potential and enzyme kinetics of benzothiazole derivatives and their non-bonded interactions with α-glucosidase and α-amylase. Med. Chem. Res.,  2016, 25(4), 805-816.
 [http://dx.doi.org/10.1007/s00044-016-1520-3]

[112]
Gollapalli, M.; Taha, M.; Javid, M.T.; Almandil, N.B.; Rahim, F.; Wadood, A.; Mosaddik, A.; Ibrahim, M.; Alqahtani, M.A.; Bamarouf, Y.A. Synthesis of benzothiazole derivatives as a potent α-glucosidase inhibitor. Bioorg. Chem.,  2019, 85(85), 33-48.
 [http://dx.doi.org/10.1016/j.bioorg.2018.12.021] [PMID: 30599411]

[113]
Maheshwari, N.; Karthikeyan, C.; Bhadada, S.V.; Verma, A.K.; Sahi, C.; Moorthy, N.S.H.N.; Trivedi, P. Design, synthesis and biological evaluation of some tetrazole acetamide derivatives as novel non-carboxylic PTP1B inhibitors. Bioorg. Chem.,  2019, 92, 103221.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103221] [PMID: 31499261]

[114]
Lad, N.P.; Manohar, Y.; Mascarenhas, M.; Pandit, Y.B.; Kulkarni, M.R.; Sharma, R.; Salkar, K.; Suthar, A.; Pandit, S.S. Methylsulfonyl benzothiazoles (MSBT) derivatives: Search for new potential antimicrobial and anticancer agents. Bioorg. Med. Chem. Lett.,  2017, 27(5), 1319-1324.
 [http://dx.doi.org/10.1016/j.bmcl.2016.08.032] [PMID: 28188067]

[115]
Patel, R.V.; Park, S.W. Access to a new class of biologically active quinoline based 1,2,4-triazoles. Eur. J. Med. Chem.,  2014, 71, 24-30.
 [http://dx.doi.org/10.1016/j.ejmech.2013.10.059] [PMID: 24269513]

[116]
Morsy, M.A.; Ali, E.M.; Kandeel, M.; Venugopala, K.N.; Nair, A.B.; Greish, K.; El-Daly, M. Screening and molecular docking of novel benzothiazole derivatives as potential antimicrobial agents. Antibiotics (Basel),  2020, 9(5), E221.
 [http://dx.doi.org/10.3390/antibiotics9050221] [PMID: 32365587]

[117]
Chugunova, E.; Boga, C.; Sazykin, I.; Cino, S.; Micheletti, G.; Mazzanti, A.; Sazykina, M.; Burilov, A.; Khmelevtsova, L.; Kostina, N. Synthesis and antimicrobial activity of novel structural hybrids of benzofuroxan and benzothiazole derivatives. Eur. J. Med. Chem.,  2015, 93, 349-359.
 [http://dx.doi.org/10.1016/j.ejmech.2015.02.023] [PMID: 25707015]

[118]
Padalkar, V.S.; Borse, B.N.; Gupta, V.D.; Phatangare, K.R.; Patil, V.S.; Umape, P.G.; Sekar, N. Synthesis and antimicrobial activity of novel 2-substituted benzimidazole, benzoxazole and benzothiazole derivatives. Arab. J. Chem.,  2012, 9, S1125-S1130.
 [http://dx.doi.org/10.1016/j.arabjc.2011.12.006]

[119]
Kumari, B.; Chauhan, K.; Trivedi, J.; Jaiswal, V.; Kanwar, S.S.; Pokharel, Y.R. Benzothiazole-based-bioconjugates with improved antimicrobial, anticancer and antioxidant potential. Chem. Sel.,  2018, 3(40), 11326-11332.
 [http://dx.doi.org/10.1002/slct.201801936]

[120]
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]

[121]
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.
 [PMID: 29061823]

[122]
Hassan, A.Y.; Sarg, M.T.; Hussein, E.M. Design, synthesis, and anticancer activity of novel benzothiazole analogues. J. Heterocycl. Chem.,  2019, 56(4), 1437-1457.
 [http://dx.doi.org/10.1002/jhet.3524]

[123]
Siddiqui, N.; Alam, M.S.; Sahu, M.; Naim, M.J.; Yar, M.S.; Alam, O. Design, synthesis, anticonvulsant evaluation and docking study of 2-[(6-substituted benzo[d]thiazol-2-ylcarbamoyl)methyl]-1-(4-substituted phenyl)isothioureas. Bioorg. Chem.,  2017, 71(71), 230-243.
 [http://dx.doi.org/10.1016/j.bioorg.2017.02.009] [PMID: 28238402]

[124]
Liu, D.C.; Zhang, H.J.; Jin, C.M.; Quan, Z.S. Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents. Molecules,  2016, 21(3), 164.
 [http://dx.doi.org/10.3390/molecules21030164] [PMID: 26938519]

[125]
Thakkar, S.S.; Thakor, P.; Ray, A.; Doshi, H.; Thakkar, V.R. Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities. Bioorg. Med. Chem.,  2017, 25(20), 5396-5406.
 [http://dx.doi.org/10.1016/j.bmc.2017.07.057] [PMID: 28789907]

[126]
Maddila, S.; Gorle, S.; Seshadri, N.; Lavanya, P.; Jonnalagadda, S.B. Synthesis, antibacterial and antifungal activity of novel benzothiazole pyrimidine derivatives. Arab. J. Chem.,  2016, 9(5), 681-687.
 [http://dx.doi.org/10.1016/j.arabjc.2013.04.003]

[127]
Gazwan, H.A. Al-Somaidaie. Synthesis, characterization and study of antibacterial activity in vitro of some hydrazones and formazan dyes containing benzothiazole moiety. Kerbala J. Pharm. Sci.,  2018, 9(3), 81-90.

[128]
Abbas, E.M.H.; Amin, K.M.; El-Hamouly, W.S.; Dawood, D.H.; Abdalla, M.M. Synthesis, anti-inflammatory and antinociceptive activity of some novel benzothiazole derivatives. Res. Chem. Intermed.,  2015, 41(4), 2537-2555.
 [http://dx.doi.org/10.1007/s11164-013-1367-x]

[129]
Ma, J.; Bao, G.; Wang, L.; Li, W.; Xu, B.; Du, B.; Lv, J.; Zhai, X.; Gong, P. Design, synthesis, biological evaluation and preliminary mechanism study of novel benzothiazole derivatives bearing indole-based moiety as potent antitumor agents. Eur. J. Med. Chem.,  2015, 96, 173-186.
 [http://dx.doi.org/10.1016/j.ejmech.2015.04.018] [PMID: 25874341]

[130]
Kumar, P.; Shrivastava, B.; Pandeya, S.N.; Tripathi, L.; Stables, J.P. Design, synthesis, and anticonvulsant evaluation of some novel 1, 3 benzothiazol-2-yl hydrazones/acetohydrazones. Med. Chem. Res.,  2012, 21, 2428-2442.
Cite As
Mini-Reviews in Medicinal Chemistry

Insight into the Synthesis, Biological Activity, and Structure-activity Relationship of Benzothiazole and Benzothiazole-hydrazone Derivatives: A Comprehensive Review

Abstract

Graphical Abstract
