Generic placeholder image

Current Topics in Medicinal Chemistry

Author(s): Lian-Shun Feng, Chuan Gao, Fa-Wu Liu, Xiao-Ping Wang* and Zhi-Liu Zhang*

DOI: 10.2174/1568026622666220428093955

DownloadDownload PDF Flyer Cite As
Recent Updates on the Anticancer Activity of Quinoxaline Hybrids (Jan. 2017-Jan. 2022)

Page: [1426 - 1441] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Cancer being one of the leading causes of death among non-communicable diseases, has already posed a heavy burden on the world health system. Chemotherapy is one of the most effective approaches for cancer treatment, but multidrug resistance, lack of efficacy, and toxic side effects hamper efficacious cancer chemotherapy, creating an urgent need to develop novel, more effective and less toxic anticancer therapeutics. Quinoxalines, as fascinating structures, constitute an important class of heterocycles in drug discovery. Quinoxaline hybrids could exert anticancer activity through diverse mechanisms and possess profound in vitro and in vivo efficacy against various cancers, including multidrug-resistant forms. Thus, quinoxaline hybrids represent useful templates for the control and eradication of cancer. The purpose of the present review article is to provide an emphasis on the recent developments (Jan. 2017-Jan. 2022) in quinoxaline hybrids with insights into their in vitro and in vivo anticancer potential as well as structure-activity relationships (SARs) to facilitate further rational design of more effective candidates.

Keywords: Quinoxaline, Hybrid molecules, Drug resistance, Anticancer, Structure-activity relationships, Mechanism of action.

Graphical Abstract

[1]
Hernández-Romero, D.; Rosete-Luna, S.; López-Monteon, A.; Chávez-Piña, A.; Pérez-Hernández, N.; Marroquín-Flores, J.; Cruz-Navarro, A.; Pesado-Gómez, G.; Morales-Morales, D.; Colorado-Peralta, R. First-row transition metal compounds containing benzimid-azole ligands: An overview of their anticancer and antitumor activity. Coord. Chem. Rev., 2021, 439, e213930.
[http://dx.doi.org/10.1016/j.ccr.2021.213930]
[2]
Hulvat, M.C. Cancer incidence and trends. Surg. Clin. North Am., 2020, 100(3), 469-481.
[http://dx.doi.org/10.1016/j.suc.2020.01.002 ] [PMID: 32402294]
[3]
Zhang, H.; Xu, H.; Ashby, C.R., Jr; Assaraf, Y.G.; Chen, Z.S.; Liu, H.M. Chemical molecular-based approach to overcome multidrug resistance in cancer by targeting P-glycoprotein (P-gp). Med. Res. Rev., 2021, 41(1), 525-555.
[http://dx.doi.org/10.1002/med.21739 ] [PMID: 33047304]
[4]
Dong, J.; Qin, Z.; Zhang, W.D.; Cheng, G.; Yehuda, A.G.; Ashby, C.R., Jr; Chen, Z.S.; Cheng, X.D.; Qin, J.J. Medicinal chemistry strate-gies to discover P-glycoprotein inhibitors: An update. Drug Resist. Updat., 2020, 49, 100681.
[http://dx.doi.org/10.1016/j.drup.2020.100681 ] [PMID: 32014648]
[5]
International Agency for Research on Cancer. Cancer Tomorrow., Available from: https://gco.iarc.fr/tomorrow/graphic-isotype?type=0&population=900&mode=population&sex=0&cancer=39&age_group=value&apc_male=0&apc_female=0
[6]
Tariq, S.; Somakala, K.; Amir, M. Quinoxaline: An insight into the recent pharmacological advances. Eur. J. Med. Chem., 2018, 143, 542-557.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.064 ] [PMID: 29207337]
[7]
Leyva-Ramos, S.; Pedraza-Alvarez, A. Quinoxaline 1,4-di-N-oxides: A review of the importance of their structure in the development of drugs against infectious diseases and cancer. Med. Chem. Res., 2021, 30(6), 1175-1184.
[http://dx.doi.org/10.1007/s00044-021-02731-8]
[8]
Ajani, O.O.; Nlebemuo, M.T.; Adekoya, J.A.; Ogunniran, K.O.; Siyanbola, T.O.; Ajanaku, C.O. Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents. Acta Pharm., 2019, 69(2), 177-196.
[http://dx.doi.org/10.2478/acph-2019-0013 ] [PMID: 31259731]
[9]
Kaushal, T.; Srivastava, G.; Sharma, A.; Singh Negi, A. An insight into medicinal chemistry of anticancer quinoxalines. Bioorg. Med. Chem., 2019, 27(1), 16-35.
[http://dx.doi.org/10.1016/j.bmc.2018.11.021 ] [PMID: 30502116]
[10]
Subran, S.K.; Paira, P. Synthesis and pharmacological applications of certain quinoxaline analogues: A review. Curr. Bioact. Compd., 2017, 13(3), 186-212.
[http://dx.doi.org/10.2174/1573407213666161108102411]
[11]
Ammaji, S.; Masthanamma, S. Synthesis, biological evaluation and structural activity relationship of quinoxaline derivatives. Int. J. Pharm. Tech., 2016, 8(4), 4947-4963.
[12]
Zheng, X.; Ma, Z.; Zhang, D. Synthesis of imidazole-based medicinal molecules utilizing the van Leusen imidazole synthesis. Pharmaceuticals (Basel), 2020, 13(3), e37.
[http://dx.doi.org/10.3390/ph13030037 ] [PMID: 32138202]
[13]
Alghamdi, S.S.; Suliman, R.S.; Almutairi, K.; Kahtani, K.; Aljatli, D. Imidazole as a promising medicinal scaffold: Current status and future direction. Drug Des. Devel. Ther., 2021, 15, 3289-3312.
[http://dx.doi.org/10.2147/DDDT.S307113 ] [PMID: 34354342]
[14]
Yadav, S.; Narasimhan, B.; Kaur, H. Perspectives of benzimidazole derivatives as anticancer agents in the new era. Anticancer. Agents Med. Chem., 2016, 16(11), 1403-1425.
[http://dx.doi.org/10.2174/1871520616666151103113412 ] [PMID: 26526461]
[15]
Ali, I.; Lone, M.N.; Aboul-Enein, H.Y. Imidazoles as potential anticancer agents. MedChemComm, 2017, 8(9), 1742-1773.
[http://dx.doi.org/10.1039/C7MD00067G ] [PMID: 30108886]
[16]
Teli, G.; Chawla, P.A. Hybridization of imidazole with various heterocycles in targeting cancer: A decade’s work. ChemistrySelect, 2021, 6(19), 4803-4836.
[http://dx.doi.org/10.1002/slct.202101038]
[17]
Patinote, C.; Deleuze-Masquéfa, C.; Kaddour, K.H.; Vincent, L.A.; Larive, R.; Zghaib, Z.; Guichou, J.F.; Assaf, M.D.; Cuq, P.; Bonnet, P.A. Imidazo[1,2-a]quinoxalines for melanoma treatment with original mechanism of action. Eur. J. Med. Chem., 2021, 212, 113031.
[http://dx.doi.org/10.1016/j.ejmech.2020.113031 ] [PMID: 33309473]
[18]
Nabbouh, A.I.; Hleihel, R.S.; Saliba, J.L.; Karam, M.M.; Hamie, M.H.; Wu, H.J.M.; Berthier, C.P.; Tawil, N.M.; Bonnet, P.A.; Deleuze-Masquefa, C.; El Hajj, H.A. Imidazoquinoxaline derivative EAPB0503: A promising drug targeting mutant nucleophosmin 1 in acute my-eloid leukemia. Cancer, 2017, 123(9), 1662-1673.
[http://dx.doi.org/10.1002/cncr.30515 ] [PMID: 28055106]
[19]
Rezaei, Z.; Mahdi Didehvar, M.; Mahdavi, M.; Azizian, H.; Hamedifar, H.; Mohammed, E.H.M.; Ostad, S.; Amini, M. Anticancer proper-ties of N-alkyl-2, 4-diphenylimidazo [1, 2-a] quinoxalin-1-amine derivatives; kinase inhibitors. Bioorg. Chem., 2019, 90, 103055.
[http://dx.doi.org/10.1016/j.bioorg.2019.103055 ] [PMID: 31220669]
[20]
Joshi, G.; Kumar, R. Anticancer activity of imidazole fused quinoxalines via human topoisomerase inhibition. J. Indian Chem. Soc., 2020, 97(8), 1217-1225.
[21]
Kumar, M.; Joshi, G.; Arora, S.; Singh, T.; Biswas, S.; Sharma, N.; Bhat, Z.R.; Tikoo, K.; Singh, S.; Kumar, R. Design and synthesis of non-covalent imidazo[1,2-a]quinoxaline-based inhibitors of EGFR and their anti-cancer assessment. Molecules, 2021, 26(5), e1490.
[http://dx.doi.org/10.3390/molecules26051490 ] [PMID: 33803355]
[22]
Singh, R.; Kumar, R.; Pandrala, M.; Kaur, P.; Gupta, S.; Tailor, D.; Malhotra, S.V.; Salunke, D.B. Facile synthesis of C6-substituted benz[4,5]imidazo[1,2-a]quinoxaline derivatives and their anticancer evaluation. Arch. Pharm. (Weinheim), 2021, 354(7), e2000393.
[http://dx.doi.org/10.1002/ardp.202000393 ] [PMID: 33749032]
[23]
Ghanbarimasir, Z.; Bekhradnia, A.; Morteza-Semnani, K.; Rafiei, A.; Razzaghi-Asl, N.; Kardan, M. Design, synthesis, biological assess-ment and molecular docking studies of new 2-aminoimida-] zole-quinoxaline hybrids as potential anticancer agents. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2018, 194, 21-35.
[http://dx.doi.org/10.1016/j.saa.2017.12.063 ] [PMID: 29310028]
[24]
Song, F.; Bian, Y.; Liu, J.; Li, Z.; Zhao, L.; Fang, J.; Lai, Y.; Zhou, M. Indole alkaloids, synthetic dimers and hybrids with potential in vivo anticancer activity. Curr. Top. Med. Chem., 2021, 21(5), 377-403.
[http://dx.doi.org/10.2174/1568026620666200908162311 ] [PMID: 32901583]
[25]
Jia, Y.; Wen, X.; Gong, Y.; Wang, X. Current scenario of indole derivatives with potential anti-drug-resistant cancer activity. Eur. J. Med. Chem., 2020, 200, 112359.
[http://dx.doi.org/10.1016/j.ejmech.2020.112359 ] [PMID: 32531682]
[26]
Dhuguru, J.; Skouta, R. Role of indole scaffolds as pharmacophores in the development of anti-lung cancer agents. Molecules, 2020, 25(7), e1615.
[http://dx.doi.org/10.3390/molecules25071615 ] [PMID: 32244744]
[27]
Ammar, Y.A.Sh. Sh El-Sharief, A.M.; Belal, A.; Abbas, S.Y.; Mohamed, Y.A.; Mehany, A.B.M.; Ragab, A. Design, synthesis, antiprolif-erative activity, molecular docking and cell cycle analysis of some novel (morpholinosulfonyl) isatins with potential EGFR inhibitory ac-tivity. Eur. J. Med. Chem., 2018, 156, 918-932.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.061 ] [PMID: 30096580]
[28]
Gu, Z.; Li, Y.; Ma, S.; Li, S.; Zhou, G.; Ding, S.; Zhang, J.; Wang, S.; Zhou, C. Synthesis, cytotoxic evaluation and DNA binding study of 9-fluoro-6H-indolo[2,3-b]quinoxaline derivatives. RSC Advances, 2017, 7(66), 41869-41879.
[http://dx.doi.org/10.1039/C7RA08138C]
[29]
Shiva Kumar, K.; Siddi Ramulu, M.; Rajesham, B.; Kumar, N.P.; Voora, V.; Kancha, R.K. FeCl3 catalysed 7-membered ring formation in a single pot: A new route to indole-fused oxepines/azepines and their cytotoxic activity. Org. Biomol. Chem., 2017, 15(20), 4468-4476.
[http://dx.doi.org/10.1039/C7OB00715A ] [PMID: 28497830]
[30]
Prasanna, G.L.; Rao, B.V.D.; Reddy, A.G.; Rao, M.V.B.; Pal, M. Lemon juice mediated reaction under ultrasound irradiation: Synthesis of indolofuroquinoxalines as potential anticancer agents. Mini Rev. Med. Chem., 2019, 19(8), 671-678.
[http://dx.doi.org/10.2174/1389557518666181029100044 ] [PMID: 30370847]
[31]
Yan, X.; Wen, J.; Zhou, L.; Fan, L.; Wang, X.; Xu, Z. Current scenario of 1,3-oxazole derivatives for anticancer activity. Curr. Top. Med. Chem., 2020, 20(21), 1916-1937.
[http://dx.doi.org/10.2174/1568026620666200624161151 ] [PMID: 32579505]
[32]
Vaidya, A.; Pathak, D.; Shah, K. 1,3,4-oxadiazole and its derivatives: A review on recent progress in anticancer activities. Chem. Biol. Drug Des., 2021, 97(3), 572-591.
[http://dx.doi.org/10.1111/cbdd.13795 ] [PMID: 32946168]
[33]
Ghoshal, T.; Patel, T.M. Anticancer activity of benzoxazole derivative (2015 onwards): A review. Future J. Pharm. Sci., 2020, 6(1), e94.
[http://dx.doi.org/10.1186/s43094-020-00115-0]
[34]
Liu, Q.Q.; Lu, K.; Zhu, H.M.; Kong, S.L.; Yuan, J.M.; Zhang, G.H.; Chen, N.Y.; Gu, C.X.; Pan, C.X.; Mo, D.L.; Su, G.F. Identification of 3-(benzazol-2-yl)quinoxaline derivatives as potent anticancer compounds: Privileged structure-based design, synthesis, and bioactive evaluation in vitro and in vivo. Eur. J. Med. Chem., 2019, 165, 293-308.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.004 ] [PMID: 30685528]
[35]
Desai, S.; Desai, V.; Shingade, S. In-vitro anti-cancer assay and apoptotic cell pathway of newly synthesized benzoxazole-N-heterocyclic hybrids as potent tyrosine kinase inhibitors. Bioorg. Chem., 2020, 94, 103382.
[http://dx.doi.org/10.1016/j.bioorg.2019.103382 ] [PMID: 31662214]
[36]
Ono, Y.; Ninomiya, M.; Kaneko, D.; Sonawane, A.D.; Udagawa, T.; Tanaka, K.; Nishina, A.; Koketsu, M. Design and synthesis of quinoxaline-1,3,4-oxadiazole hybrid derivatives as potent inhibitors of the anti-apoptotic Bcl-2 protein. Bioorg. Chem., 2020, 104, 104245.
[http://dx.doi.org/10.1016/j.bioorg.2020.104245 ] [PMID: 32911196]
[37]
Ganguly, S.; Jacob, S.K. Therapeutic outlook of pyrazole analogs: A mini review. Mini Rev. Med. Chem., 2017, 17(11), 959-983.
[http://dx.doi.org/10.2174/1389557516666151120115302 ] [PMID: 26586126]
[38]
Chauhan, S.; Paliwal, S.; Chauhan, R. Anticancer activity of pyrazole via different biological mechanisms. Synth. Commun., 2014, 44, 1333-1374.
[http://dx.doi.org/10.1080/00397911.2013.837186]
[39]
Contreras, J.I.; Ezell, E.L.; Garrison, J.C.; Kizhake, S.; Mallareddy, J.R.; Napoleon, J.V.; Natarajan, A.; Singh, S.; Sonawane, Y.A. Struc-ture activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy. Eur. J. Med. Chem., 2021, 222, e113579.
[http://dx.doi.org/10.1016/j.ejmech.2021.113579]
[40]
Kim, S.C.; Boggu, P.R.; Yu, H.N.; Ki, S.Y.; Jung, J.M.; Kim, Y.S.; Park, G.M.; Ma, S.H.; Kim, I.S.; Jung, Y.H. Synthesis and biological evaluation of quinoxaline derivatives as specific c-Met kinase inhibitors. Bioorg. Med. Chem. Lett., 2020, 30(13), 127189.
[http://dx.doi.org/10.1016/j.bmcl.2020.127189 ] [PMID: 32371098]
[41]
El Saeed, H.S.; Bayoumi, A.H.; Sarg, M.T.; Ghiaty, A.H. Synthesis of novel triazoloquinoxaline-pyrazole hybrids as antiproliferatives, EGFR inhibitors, and apoptosis inducers. J. Heterocycl. Chem., 2020, 57(12), 4358-4372.
[http://dx.doi.org/10.1002/jhet.4144]
[42]
Barkov, A.Y.; Korotaev, V.Y.; Kutyashev, I.B.; Sosnovskikh, V.Y.; Ulitko, M.V.; Zimnitskiy, N.S. An expedient synthesis of novel spiro[indenoquinoxaline-pyrrolizidine]-pyrazole conjugates with anticancer activity from 1,5-diarylpent-4-ene-1,3-diones through the 1,3-dipolar cycloaddition/cyclocondensation sequence. New J. Chem., 2020, 44(37), 16185-16199.
[http://dx.doi.org/10.1039/D0NJ02817G]
[43]
Gao, F.; Zhang, X.; Wang, T.; Xiao, J. Quinolone hybrids and their anti-cancer activities: An overview. Eur. J. Med. Chem., 2019, 165, 59-79.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.017 ] [PMID: 30660827]
[44]
Man, R.J.; Jeelani, N.; Zhou, C.; Yang, Y.S. Recent progress in the development of quinoline derivatives for the exploitation of anti-cancer agents. Anticancer. Agents Med. Chem., 2021, 21(7), 825-838.
[http://dx.doi.org/10.2174/1871520620666200516150345 ] [PMID: 32416703]
[45]
Saravana Mani, K.; Kaminsky, W.; Rajendran, S.P. A facile atom economic one pot multicomponent synthesis of bioactive spiro-indenoquinoxaline pyrrolizines as potent antioxidants and anti-cancer agents. New J. Chem., 2018, 42(1), 301-310.
[http://dx.doi.org/10.1039/C7NJ02993D]
[46]
Gothandam, K.M.; Mohan, P.S.; Saravanan, A.; Shankar, R.; Shyamsivappan, S.; Suresh, T.; Vivek, R. Novel phenyl and thiophene dispiro indenoquinoxaline pyrrolidine quinolones induced apoptosis via G1/S and G2/M phase cell cycle arrest in MCF-7 cells. New J. Chem., 2020, 44(35), 15031-15045.
[http://dx.doi.org/10.1039/D0NJ02588G]
[47]
Saravana Mani, K.; Murugesapandian, B.; Kaminsky, W.; Rajendran, S.P. Enantioselective approach towards the synthesis of spiro-indeno[1,2-b]quinoxaline pyrrolothiazoles as antioxidant and antiproliferative. Tetrahedron Lett., 2018, 59(30), 2921-2929.
[http://dx.doi.org/10.1016/j.tetlet.2018.06.035]
[48]
Lv, K.; Chen, W.; Chen, D.; Mou, J.; Zhang, H.; Fan, T.; Li, Y.; Cao, D.; Wang, X.; Chen, L.; Shen, J.; Pei, D.; Xiong, B. Rational design and evaluation of 6-(pyrimidin-2-ylamino)-3,4-dihydro-] quinoxalin-2(1H)-ones as polypharmacological inhibitors of BET and kinases. J. Med. Chem., 2020, 63(17), 9787-9802.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00962 ] [PMID: 32787081]
[49]
Liu, J.; Yang, D.; Yang, X.; Nie, M.; Wu, G.; Wang, Z.; Li, W.; Liu, Y.; Gong, P. Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors. Bioorg. Med. Chem., 2017, 25(16), 4475-4486.
[http://dx.doi.org/10.1016/j.bmc.2017.06.037 ] [PMID: 28716639]
[50]
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]
[51]
Pawar, S.; Kumar, K.; Gupta, M.K.; Rawal, R.K. Synthetic and medicinal perspective of fused-thiazoles as anticancer agents. Anticancer. Agents Med. Chem., 2021, 21(11), 1379-1402.
[http://dx.doi.org/10.2174/1871520620666200728133017 ] [PMID: 32723259]
[52]
Abbas, H.S.; Al-Marhabi, A.R.M.; Ammar, Y.A. Design, synthesis and biological evaluation of 2,3-disubstituted and fused quinoxalines as potential anticancer and antimicrobial agents. Acta Pol. Pharm., 2017, 74(2), 445-458.
[PMID: 29624250]
[53]
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]
[54]
Babu, L.T.; Jadhav, G.R.; Paira, P. Luminescent bis(benzo[d]] thiazolyl)quinoxaline: Facile synthesis, nucleic acid and protein BSA interaction, live-cell imaging, biopharmaceutical research and can-cer theranostic application. RSC Advances, 2019, 9(16), 8748-8752.
[http://dx.doi.org/10.1039/C9RA01498E]
[55]
Wen, X.; Zhou, Y.; Zeng, J.; Liu, X. Recent development of 1,2,4-triazole-containing compounds as anticancer agents. Curr. Top. Med. Chem., 2020, 20(16), 1441-1460.
[http://dx.doi.org/10.2174/1568026620666200128143230 ] [PMID: 31994462]
[56]
Kaur, R.; Dwivedi, A.R.; Kumar, B.; Kumar, V. Recent developments on 1,2,4-triazole nucleus in anticancer compounds: A review. Anticancer. Agents Med. Chem., 2016, 16(4), 465-489.
[http://dx.doi.org/10.2174/1871520615666150819121106 ] [PMID: 26286663]
[57]
El-Adl, K.; El-Helby, A.A.; Sakr, H.; Elwan, A. Design, synthesis, molecular docking and anti-proliferative evaluations of [1,2,4]triazolo[4,3-a]quinoxaline derivatives as DNA intercalators and Topoisomerase II inhibitors. Bioorg. Chem., 2020, 105, 104399.
[http://dx.doi.org/10.1016/j.bioorg.2020.104399 ] [PMID: 33113414]
[58]
Ali, I.; Lee, J.; Go, A.; Choi, G.; Lee, K. Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment. Bioorg. Med. Chem. Lett., 2017, 27(20), 4606-4613.
[http://dx.doi.org/10.1016/j.bmcl.2017.09.025 ] [PMID: 28939121]
[59]
El-Adl, K.; El-Helby, A.G.A.; Sakr, H.; Elwan, A. Triazolo[4,3-a]quinoxaline and [1,2,4]triazolo[4,3-a]quinoxaline-1-thiol-derived DNA intercalators: Design, synthesis, molecular docking, in silico ADMET profiles and anti-proliferative evaluations. New J. Chem., 2021, 45(2), 881-897.
[http://dx.doi.org/10.1039/D0NJ02990D]
[60]
Kaneko, D.; Ninomiya, M.; Yoshikawa, R.; Ono, Y.; Sonawane, A.D.; Tanaka, K.; Nishina, A.; Koketsu, M. Synthesis of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as potent antiproliferative agents via a hybrid pharmacophore approach. Bioorg. Chem., 2020, 104, 104293.
[http://dx.doi.org/10.1016/j.bioorg.2020.104293 ] [PMID: 33010622]
[61]
Eissa, I.H.; Metwaly, A.M.; Belal, A.; Mehany, A.B.M.; Ayyad, R.R.; El-Adl, K.; Mahdy, H.A.; Taghour, M.S.; El-Gamal, K.M.A.; El-Sawah, M.E.; Elmetwally, S.A.; Elhendawy, M.A.; Radwan, M.M.; ElSohly, M.A. Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors. Arch. Pharm. (Weinheim), 2019, 352(11), e1900123.
[http://dx.doi.org/10.1002/ardp.201900123 ] [PMID: 31463953]
[62]
Alsaif, N.A.; Elwan, A.; Alanazi, M.M.; Obaidullah, A.J.; Alanazi, W.A.; Alasmari, A.F.; Albassam, H.; Mahdy, H.A.; Taghour, M.S. Design, synthesis and molecular docking of new [1,2,4] triazolo[4,3-a]quinoxaline derivatives as anticancer agents targeting VEGFR-2 kinase. Mol. Divers., 2021. Epub ahead of print
[http://dx.doi.org/10.1007/s11030-021-10303-6 ] [PMID: 34460053]
[63]
Alanazi, M.M.; Mahdy, H.A.; Alsaif, N.A.; Obaidullah, A.J.; Alkahtani, H.M.; Al-Mehizia, A.A.; Alsubaie, S.M.; Dahab, M.A.; Eissa, I.H. New bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation. Bioorg. Chem., 2021, 112, 104949.
[http://dx.doi.org/10.1016/j.bioorg.2021.104949 ] [PMID: 34023640]
[64]
Abbass, E.M.; Khalil, A.K.; Mohamed, M.M.; Eissa, I.H.; El-Naggar, A.M. Design, efficient synthesis, docking studies, and anticancer evaluation of new quinoxalines as potential intercalative Topo II inhibitors and apoptosis inducers. Bioorg. Chem., 2020, 104, 104255.
[http://dx.doi.org/10.1016/j.bioorg.2020.104255 ] [PMID: 32927130]
[65]
Desplat, V.; Vincenzi, M.; Lucas, R.; Moreau, S.; Savrimoutou, S.; Rubio, S.; Pinaud, N.; Bigat, D.; Enriquez, E.; Marchivie, M.; Routier, S.; Sonnet, P.; Rossi, F.; Ronga, L.; Guillon, J. Synthesis and antiproliferative effect of ethyl 4-(4-substitutedpiperidin-1-yl)]benzylpyrrolo[1,2-a]quinoxalinecarboxylate derivatives on human leukemic cells. ChemMedChem, 2017, 12(12), 940-953.
[http://dx.doi.org/10.1002/cmdc.201700049 ] [PMID: 28218826]
[66]
Abu-Hashem, A.A.; Al-Hussain, S.A.; Zaki, M.E.A. Design, synthesis and anticancer activity of new polycyclic: Imidazole, thiazine, oxathiine, pyrrolo-quinoxaline and thienotriazolopyrimidine derivatives. Molecules, 2021, 26(7), e2031.
[http://dx.doi.org/10.3390/molecules26072031 ] [PMID: 33918322]
[67]
Kim, J.; Cha, H.M.; Park, M.; Singh, D.K.; Bea, G.H.; Kim, S.H.; Kim, I. Expanding the chemical space: Discovery of new anticancer 3-arylbenzofuran derivatives. J. Heterocycl. Chem., 2020, 57, 3279-3293.
[http://dx.doi.org/10.1002/jhet.4043]
[68]
Zhang, N.; Yu, Z.; Yang, X.; Zhou, Y.; Tang, Q.; Hu, P.; Wang, J.; Zhang, S.L.; Wang, M.W.; He, Y. Difuran-substituted quinoxalines as a novel class of PI3Kα H1047R mutant inhibitors: Synthesis, biological evaluation and structure-activity relationship. Eur. J. Med. Chem., 2018, 157, 37-49.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.061 ] [PMID: 30071408]
[69]
Lewis, T.R.; Smith, J.; Griffin, K.; Aguiar, S.; Rueb, K.F.; Holmberg-Douglas, N.; Sampson, E.M.; Tomasetti, S.; Rodriguez, S.; Stachura, D.L.; Arpin, C.C. NHD2-15, a novel antagonist of Growth Factor Receptor-Bound Protein-2 (GRB2), inhibits leukemic proliferation. PLoS One, 2020, 15(8), e0236839.
[http://dx.doi.org/10.1371/journal.pone.0236839 ] [PMID: 32780746]
[70]
Aiello, F.; Carullo, G.; Giordano, F.; Spina, E.; Nigro, A.; Garofalo, A.; Tassini, S.; Costantino, G.; Vincetti, P.; Bruno, A.; Radi, M. Iden-tification of breast cancer inhibitors specific for G protein-coupled estrogen receptor (GPER)-expressing cells. ChemMedChem, 2017, 12(16), 1279-1285.
[http://dx.doi.org/10.1002/cmdc.201700145 ] [PMID: 28520140]
[71]
Ma, X.; Wang, D.; Wei, G.; Zhou, Q.; Gan, X. Synthesis and anticancer activity of chalcone-quinoxalin conjugates. Synth. Commun., 2021, 51(9), 1363-1372.
[http://dx.doi.org/10.1080/00397911.2021.1881124]
[72]
Gobouri, A.A. Synthesis and biological evaluation of some N-substituted quinoxaline derivatives as antitumor agents. Russ. J. Bioorganic Chem., 2020, 46(3), 409-416.
[http://dx.doi.org/10.1134/S1068162020030097]
[73]
Aboelmagd, A.; Alotaibi, S.H.; Bayes, S.M.E.; Elsayed, G.M.; Ali, I.A.I.; Fathalla, W.; Pottoo, F.H.; Khan, F.A. Synthesis and anti-proliferative activity of new N-pentylquinoxaline carboxamides and their O-regioisomer. ChemistrySelect, 2020, 5, 13439-13453.
[http://dx.doi.org/10.1002/slct.202003024]
[74]
Aboelmagd, A.; Rayes, S.M.; Gomaa, M.S.; Ali, I.A.I.; Fathalla, W.; Pottoo, F.H.; Khan, F.A.; Khalifa, M.E. The synthesis and antiprolif-erative activity of new N-allyl quinoxalinecarboxamides and their O-regioisomers. New J. Chem., 2021, 45, 831-849.
[http://dx.doi.org/10.1039/D0NJ03672B]
[75]
Bayoumi, A.H.; Ghiaty, A.H.; El-Gilil, S.M.A.; Husseiny, E.M.; Ebrahim, M.A. Exploration of quinoxaline derivatives as antimicrobial and anticancer agents. J. Heterocycl. Chem., 2019, 56, 3215-3235.
[http://dx.doi.org/10.1002/jhet.3716]
[76]
Ayoup, M.S.; Abu-Serie, M.M.; Awad, L.F.; Teleb, M.; Ragab, H.M.; Amer, A. Halting colorectal cancer metastasis via novel dual nano-molar MMP-9/MAO-A quinoxaline-based inhibitors; design, synthesis, and evaluation. Eur. J. Med. Chem., 2021, 222, 113558.
[http://dx.doi.org/10.1016/j.ejmech.2021.113558 ] [PMID: 34116327]
[77]
Alanazi, M.M.; Elkady, H.; Alsaif, N.A.; Obaidullah, A.J.; Alanazi, W.A.; Al-Hossaini, A.M.; Alharbi, M.A. Eissa, Ibrahim, H.; Dahab, M.A. Discovery of new quinoxaline-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: Design, synthesis, and in sil-ico study. J. Mol. Struct., 2022, 1253, e132220.
[http://dx.doi.org/10.1016/j.molstruc.2021.132220]
[78]
Eissa, I.H.; El-Naggar, A.M.; El-Sattar, N.E.A.A.; Youssef, A.S.A. Design and discovery of novel quinoxaline derivatives as dual DNA intercalators and Topoisomerase II inhibitors. Anticancer. Agents Med. Chem., 2018, 18(2), 195-209.
[http://dx.doi.org/10.2174/1871520617666170710182405 ] [PMID: 28699490]
[79]
Maranhão, S.S.; Moura, A.F.; Oliveira, A.C.A.; Lima, D.J.B.; Barros-Nepomuceno, F.W.A.; Paier, C.R.K.; Pinheiro, A.C.; Nogueira, T.C.M.; de Souza, M.V.N.; Pessoa, C. Synthesis of PJOV56, a new quinoxalinyl-hydrazone derivative able to induce autophagy and apoptosis in colorectal cancer cells, and related compounds. Bioorg. Med. Chem. Lett., 2020, 30(2), 126851.
[http://dx.doi.org/10.1016/j.bmcl.2019.126851 ] [PMID: 31836446]
[80]
Abdallah, A.E.; Mabrouk, R.R.; Al Ward, M.M.S.; Eissa, S.I.; Elkaeed, E.B.; Mehany, A.B.M.; Abo-Saif, M.A.; El-Feky, O.A.; Alesawy, M.S.; El-Zahabi, M.A. Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers de-signed as VEGFR-2 inhibitors. J. Enzyme Inhib. Med. Chem., 2022, 37(1), 573-591.
[http://dx.doi.org/10.1080/14756366.2021.2017911 ] [PMID: 35012403]