Heterocyclic Compounds: Importance in Anticancer Drug Discovery

Naresh      Kumar; Nidhi      Goel
doi:10.2174/1871520622666220404082648
Abstract

Cancer, a crucial global health problem, is characterized by abnormal cell division and uncontrolled growth. According to WHO, cancer is the second leading cause of global deaths and accounted for approximately 9.6 million deaths or one in six deaths in 2018. The National Cancer Registry Programme Report 2020, released by the ICMRIndia, estimated that there would be 13,90,000 cases of cancer in India in 2020 and that this number is likely to rise to 15,70,000 by 2025. In spite of several anti-cancer drugs, cancer cannot be cured completely, especially at late stages. In the current era, almost every person is suffering from some kind of disease. Thus, it is the necessity of time to develop novel, potent bioactive molecules. Many researchers are working on the development of new lead molecules or finding a new biological target for the betterment of human beings. However, heterocycles are constantly being used for the discovery of new lead molecules. Many of the clinically approved drugs contain the heterocyclic core as these molecules show exhilarating pharmaceutical properties, including anti-cancer agents such as methotrexate, vinblastine, vincristine, daunorubicin, 5-fluorouracil, doxorubicin, etc. Thus, heterocyclic compounds provide a fascinating research area for the design and development of anti-cancer drug(s). Herein, we focused on the natural as well as synthetic anti-cancer heterocyclic compounds. Furthermore, efforts have been made toward the mechanism of action of selected heterocyclic anti-cancer compounds.
Keywords: Heteroatoms, heterocyclic rings, cancer, chemotherapy, anticancer agents, drug discovery.
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[1] 
Seyfried, T.N.; Huysentruyt, L.C. On the origin of cancer metastasis. Crit. Rev. Oncog.,  2013, 18(1-2), 43-73.
[http://dx.doi.org/10.1615/CritRevOncog.v18.i1-2.40] [PMID: 23237552] 
[2] 
Kumar, N.; Gupta, S.; Chand Yadav, T.; Pruthi, V.; Kumar Varadwaj, P.; Goel, N. Extrapolation of phenolic compounds as multi-target agents against cancer and inflammation. J. Biomol. Struct. Dyn.,  2019, 37(9), 2355-2369.
[http://dx.doi.org/10.1080/07391102.2018.1481457] [PMID: 30047324] 
[3] 
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338] 
[4] 
Martins, P.; Jesus, J.; Santos, S.; Raposo, L.R.; Roma-Rodrigues, C.; Baptista, P.V.; Fernandes, A.R. Heterocyclic anticancer compounds: Recent advances and the paradigm shift towards the use of nanomedicine’s tool box. Molecules,  2015, 20(9), 16852-16891.
[http://dx.doi.org/10.3390/molecules200916852] [PMID: 26389876] 
[5] 
Alvárez-Builla, J.; Barluenga, J. Heterocyclic compounds: An introduction. Mod. Heterocycl. Chem.,  2011, 1, 1-9.
[6] 
Azab, M.E.; Youssef, M.M.; El-Bordany, E.A. Synthesis and antibacterial evaluation of novel heterocyclic compounds containing a sulfonamido moiety. Molecules,  2013, 18(1), 832-844.
[http://dx.doi.org/10.3390/molecules18010832] [PMID: 23344196] 
[7] 
Cao, X.; Sun, Z.; Cao, Y.; Wang, R.; Cai, T.; Chu, W.; Hu, W.; Yang, Y. Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J. Med. Chem.,  2014, 57(9), 3687-3706.
[http://dx.doi.org/10.1021/jm4016284] [PMID: 24564525] 
[8] 
Chen, Y.; Yu, K.; Tan, N.Y.; Qiu, R.H.; Liu, W.; Luo, N.L.; Tong, L.; Au, C.T.; Luo, Z.Q.; Yin, S.F. Synthesis, characterization and anti-proliferative activity of heterocyclic hypervalent organoantimony compounds. Eur. J. Med. Chem.,  2014, 79, 391-398.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.026] [PMID: 24747750] 
[9] 
El-Salam, N.M.A.; Mostafa, M.S.; Ahmed, G.A.; Alothman, O.Y. Synthesis and antimicrobial activities of some new heterocyclic compounds based on 6-chloropyridazine-3 (2h)-thione. J. Chem.,  2013, 2013, 1-8.
[http://dx.doi.org/10.1155/2013/890617] 
[10] 
El-Sawy, E.R.; Ebaid, M.S.; Abo-Salem, H.M.; Al-Sehemi, A.G.; Mandour, A.H. Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of some new 4,6-dimethoxy-5-(heterocycles)benzofuran starting from naturally occurring visnagin. Arab. J. Chem.,  2013, 7(6), 914-923.
[http://dx.doi.org/10.1016/j.arabjc.2012.12.041] 
[11] 
El-Sawy, E.R.; Mandour, A.H.; El-Hallouty, S.M.; Shaker, K.H.; Abo-Salem, H.M. Synthesis, antimicrobial and anticancer activities of some new N-methylsulphonyl and N-benzenesulphonyl-3-indolyl heterocycles. 1st cancer update. Arab. J. Chem.,  2013, 6(1), 67-78.
[http://dx.doi.org/10.1016/j.arabjc.2012.04.003] 
[12] 
Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K.K.; Jonnalagadda, S.B. A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules,  2020, 25(8), 1-42.
[http://dx.doi.org/10.3390/molecules25081909] [PMID: 32326131] 
[13] 
Mabkhot, Y.N.; Barakat, A.; Al-Majid, A.M.; Alshahrani, S.; Yousuf, S.; Choudhary, M.I. Synthesis, reactions and biological activity of some new bis-heterocyclic ring compounds containing sulphur atom. Chem. Cent. J.,  2013, 7(1), 112-120.
[http://dx.doi.org/10.1186/1752-153X-7-112] [PMID: 23829861] 
[14] 
Salem, M.S.; Sakr, S.I.; El-Senousy, W.M.; Madkour, H.M.F. Synthesis, antibacterial, and antiviral evaluation of new heterocycles containing the pyridine moiety. Arch. Pharm. (Weinheim),  2013, 346(10), 766-773.
[http://dx.doi.org/10.1002/ardp.201300183] [PMID: 24105721] 
[15] 
Ferlay, J.; Ervik, M.; Lam, F.; Colombet, M.; Mery, L.; Piñeros, M.; Znaor, A.; Soerjomataram, I.; Bray, F. Global Cancer Observatory: Cancer Today;  International Agency for Research on Cancer: Lyon, France, 2020. Available from: https://gco.iarc.fr/today
[16] 
Dua, R.; Shrivastava, S.; Sonwane, S.K.; Srivastava, S.K. Pharmacological significance of synthetic heterocycles scaffold : A review. Adv. Biol. Res. (Faisalabad),  2011, 5, 120-144.
[17] 
Gomtsyan, A. Heterocycles in drugs and drug discovery. Chem. Heterocycl. Compd.,  2012, 48(1), 7-10.
[http://dx.doi.org/10.1007/s10593-012-0960-z] 
[18] 
Broughton, H.B.; Watson, I.A. Selection of heterocycles for drug design. J. Mol. Graph. Model.,  2004, 23(1), 51-58.
[http://dx.doi.org/10.1016/j.jmgm.2004.03.016] [PMID: 15331053] 
[19] 
Pearce, S. The importance of heterocyclic compounds in anti-cancer drug design. DDW,  2017, 2017, 66-70.
[20] 
Li, X.; He, L.; Chen, H.; Wu, W.; Jiang, H. Copper-catalyzed aerobic C(sp2)-H functionalization for C-N bond formation: Synthesis of pyrazoles and indazoles. J. Org. Chem.,  2013, 78(8), 3636-3646.
[http://dx.doi.org/10.1021/jo400162d] [PMID: 23547954] 
[21] 
Kerru, N.; Singh, P.; Koorbanally, N.; Raj, R.; Kumar, V. Recent advances (2015-2016) in anticancer hybrids. Eur. J. Med. Chem.,  2017, 142, 179-212.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.033] [PMID: 28760313] 
[22] 
Kerru, N.; Bhaskaruni, S.V.H.S.; Gummidi, L.; Maddila, S.N.; Maddila, S.; Jonnalagadda, S.B. Recent advances in heterogeneous catalysts for the synthesis of imidazole derivatives. Synth. Commun.,  2019, 49(19), 2437-2459.
[http://dx.doi.org/10.1080/00397911.2019.1639755] 
[23] 
Santos, C.M.M.; Freitas, M.; Fernandes, E. A comprehensive review on xanthone derivatives as α-glucosidase inhibitors. Eur. J. Med. Chem.,  2018, 157, 1460-1479.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.073] [PMID: 30282319] 
[24] 
Dos Santos, F.A.; Pereira, M.C.; de Oliveira, T.B.; Mendonça, Junior, F.J.B.; de Lima, M.D.C.A.; Pitta, M.G.D.R.; Pitta, I.D.R.; de Melo Rêgo, M.J.B.; da Rocha Pitta, M.G. Anticancer properties of thiophene derivatives in breast cancer MCF-7 cells. Anticancer Drugs,  2018, 29(2), 157-166.
[http://dx.doi.org/10.1097/CAD.0000000000000581] [PMID: 29256900] 
[25] 
Kalaria, P.N.; Karad, S.C.; Raval, D.K. A review on diverse heterocyclic compounds as the privileged scaffolds in antimalarial drug discovery. Eur. J. Med. Chem.,  2018, 158, 917-936.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.040] [PMID: 30261467] 
[26] 
Almerico, A.M.; Diana, P.; Barraja, P.; Dattolo, G.; Mingoia, F.; Loi, A.G.; Scintu, F.; Milia, C.; Puddu, I.; La Colla, P. Glycosidopyrroles. Part 1. acyclic derivatives: 1-(2-hydroxyethoxy)methylpyrroles as potential anti-viral agents. Farmaco,  1998, 53(1), 33-40.
[http://dx.doi.org/10.1016/S0014-827X(97)00002-5] [PMID: 9543724] 
[27] 
Deidda, D.; Lampis, G.; Fioravanti, R.; Biava, M.; Porretta, G.C.; Zanetti, S.; Pompei, R. Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob. Agents Chemother.,  1998, 42(11), 3035-3037.
[http://dx.doi.org/10.1128/AAC.42.11.3035] [PMID: 9797251] 
[28] 
Neamati, N.; Mazumder, A.; Sunder, S.; Owen, J.M.; Tandon, M.; Lown, J.W.; Pommier, Y. Highly potent synthetic polyamides, bisdistamycins, and lexitropsins as inhibitors of human immunodeficiency virus type 1 integrase. Mol. Pharmacol.,  1998, 54(2), 280-290.
[http://dx.doi.org/10.1124/mol.54.2.280] [PMID: 9687569] 
[29] 
Ferreira, P.M.T.; Maia, H.L.S.; Monteiro, L.S. Synthesis of 2,3,5-substituted pyrrole derivatives. Tetrahedron Lett.,  2002, 43(25), 4491-4493.
[http://dx.doi.org/10.1016/S0040-4039(02)00810-9] 
[30] 
Schaefer, E.J.; McNamara, J.R.; Tayler, T.; Daly, J.A.; Gleason, J.L.; Seman, L.J.; Ferrari, A.; Rubenstein, J.J. Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Am. J. Cardiol.,  2004, 93(1), 31-39.
[http://dx.doi.org/10.1016/j.amjcard.2003.09.008] [PMID: 14697462] 
[31] 
Prommer, E. Role of codeine in palliative care. J. Opioid. Manag.,  2011, 7(5), 401-406.
[http://dx.doi.org/10.5055/jom.2011.0081] [PMID: 22165039] 
[32] 
Kaushik, N.K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C.H.; Verma, A.K.; Choi, E.H. Biomedical importance of indoles. Molecules,  2013, 18(6), 6620-6662.
[http://dx.doi.org/10.3390/molecules18066620] [PMID: 23743888] 
[33] 
Vitaku, E.; Smith, D.T.; Njardarson, J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J. Med. Chem.,  2014, 57(24), 10257-10274.
[http://dx.doi.org/10.1021/jm501100b] [PMID: 25255204] 
[34] 
Ajani, O.O.; Audu, O.Y.; Aderohunmu, D.V.; Owolabi, F.E.; Olomieja, O.A. Undeniable pharmacological potentials of quinazoline motifs in therapeutic medicine. Am. J. Drug Discovery Dev.,  2017, 7(1), 1-24.
[http://dx.doi.org/10.3923/ajdd.2017.1.24] 
[35] 
Zhu, S.L.; Wu, Y.; Liu, C.J.; Wei, C.Y.; Tao, J.C.; Liu, H.M. Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents. Eur. J. Med. Chem.,  2013, 65, 70-82.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.044] [PMID: 23693151] 
[36] 
Heravi, M.M.; Talaei, B. Diketene as privileged synthon in the syntheses of heterocycles Part 1: Four- and five-membered ring heterocycles. Adv. Heterocycl. Chem.,  2017, 122, 43-114.
[http://dx.doi.org/10.1016/bs.aihch.2016.10.003] 
[37] 
Hosseinzadeh, Z.; Ramazani, A.; Razzaghi-Asl, N. Anti-cancer Nitrogen-containing heterocyclic compounds. Curr. Org. Chem.,  2018, 22(23), 2256-2279.
[http://dx.doi.org/10.2174/1385272822666181008142138] 
[38] 
Chadha, N.; Silakari, O. Indoles as therapeutics of interest in medicinal chemistry: Bird’s eye view. Eur. J. Med. Chem.,  2017, 134, 159-184.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.003] [PMID: 28412530] 
[39] 
Dadashpour, S.; Emami, S. Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms. Eur. J. Med. Chem.,  2018, 150, 9-29.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.065] [PMID: 29505935] 
[40] 
Wan, Y.; Li, Y.; Yan, C.; Yan, M.; Tang, Z. Indole: A privileged scaffold for the design of anti-cancer agents. Eur. J. Med. Chem.,  2019, 183111691
[http://dx.doi.org/10.1016/j.ejmech.2019.111691] [PMID: 31536895] 
[41] 
Aggarwal, B.B.; Ichikawa, H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle,  2005, 4(9), 1201-1215.
[http://dx.doi.org/10.4161/cc.4.9.1993] [PMID: 16082211] 
[42] 
Kaur, K.; Jaitak, V. Recent development in indole derivatives as anticancer agents for breast cancer. Anticancer. Agents Med. Chem.,  2019, 19(8), 962-983.
[http://dx.doi.org/10.2174/1871520619666190312125602] [PMID: 30864529] 
[43] 
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, 200112359
[http://dx.doi.org/10.1016/j.ejmech.2020.112359] [PMID: 32531682] 
[44] 
Abrams, T.J.; Lee, L.B.; Murray, L.J.; Pryer, N.K.; Cherrington, J.M. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol. Cancer Ther.,  2003, 2(5), 471-478.
[PMID: 12748309] 
[45] 
Abrams, T.J.; Murray, L.J.; Pesenti, E.; Holway, V.W.; Colombo, T.; Lee, L.B.; Cherrington, J.M.; Pryer, N.K. Preclinical evaluation of the tyrosine kinase inhibitor SU11248 as a single agent and in combination with “standard of care” therapeutic agents for the treatment of breast cancer. Mol. Cancer Ther.,  2003, 2(10), 1011-1021.
[PMID: 14578466] 
[46] 
Mendel, D.B.; Laird, A.D.; Xin, X.; Louie, S.G.; Christensen, J.G.; Li, G.; Schreck, R.E.; Abrams, T.J.; Ngai, T.J.; Lee, L.B.; Murray, L.J.; Carver, J.; Chan, E.; Moss, K.G.; Haznedar, J.O.; Sukbuntherng, J.; Blake, R.A.; Sun, L.; Tang, C.; Miller, T.; Shirazian, S.; McMahon, G.; Cherrington, J.M. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: Determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res.,  2003, 9(1), 327-337.
[PMID: 12538485] 
[47] 
Le Tourneau, C.; Raymond, E.; Faivre, S. Sunitinib: A novel tyrosine kinase inhibitor. A brief review of its therapeutic potential in the treatment of renal carcinoma and gastrointestinal stromal tumors (GIST). Ther. Clin. Risk Manag.,  2007, 3(2), 341-348.
[http://dx.doi.org/10.2147/tcrm.2007.3.2.341] [PMID: 18360643] 
[48] 
Gregory, R.K.; Smith, I.E. Vinorelbine-a clinical review. Br. J. Cancer,  2000, 82(12), 1907-1913.
[PMID: 10864196] 
[49] 
Wang, L.G.; Liu, X.M.; Kreis, W.; Budman, D.R. The effect of antimicrotubule agents on signal transduction pathways of apoptosis: A review. Cancer Chemother. Pharmacol.,  1999, 44(5), 355-361.
[http://dx.doi.org/10.1007/s002800050989] [PMID: 10501907] 
[50] 
Ruvolo, P.P.; Deng, X.; May, W.S. Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia,  2001, 15(4), 515-522.
[http://dx.doi.org/10.1038/sj.leu.2402090] [PMID: 11368354] 
[51] 
Himes, R.H.; Kersey, R.N.; Heller-Bettinger, I.; Samson, F.E. Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Res.,  1976, 36(10), 3798-3802.
[PMID: 954003] 
[52] 
Drukman, S.; Kavallaris, M. Microtubule alterations and resistance to tubulin-binding agents (review). Int. J. Oncol.,  2002, 21(3), 621-628.
[http://dx.doi.org/10.3892/ijo.21.3.621] [PMID: 12168109] 
[53] 
Moudi, M.; Go, R.; Yien, C.Y.S.; Nazre, M. Vinca alkaloids. Int. J. Prev. Med.,  2013, 4(11), 1231-1235.
[PMID: 24404355] 
[54] 
Almatar, M.; Makky, E.A. Chemotherapeutic agents: Taxol and vincristine isolated from endophytic fungi. Int. J. Curr. Pharm. Rev. Res.,  2015, 6(1), 80-88.
[55] 
Mohareb, R.M.; El-Sayed, N.N.E.; Abdelaziz, M.A. Uses of cyanoacetylhydrazine in heterocyclic synthesis: Novel synthesis of pyrazole derivatives with anti-tumor activities. Molecules,  2012, 17(7), 8449-8463.
[http://dx.doi.org/10.3390/molecules17078449] [PMID: 22790561] 
[56] 
Chauhan, M.; Kumar, R. Medicinal attributes of pyrazolo[3,4-d]pyrimidines: A review. Bioorg. Med. Chem.,  2013, 21(18), 5657-5668.
[http://dx.doi.org/10.1016/j.bmc.2013.07.027] [PMID: 23932070] 
[57] 
Ansari, A.; Ali, A.; Asif, M.; Shamsuzzaman, S. Review: Biologically active pyrazole derivatives. New J. Chem.,  2017, 41(1), 16-41.
[http://dx.doi.org/10.1039/C6NJ03181A] 
[58] 
Shukla, P.; Sharma, A.; Fageria, L.; Chowdhury, R. Novel spiro/non-spiro pyranopyrazoles: Eco-friendly synthesis, in-vitro anticancer activity, DNA binding, and in-silico docking studies. Curr. Bioact. Compd.,  2019, 15(2), 257-267.
[http://dx.doi.org/10.2174/1573407213666170828165512] 
[59] 
Saleh, N.M.; El-Gazzar, M.G.; Aly, H.M.; Othman, R.A. Novel anticancer fused pyrazole derivatives as EGFR and VEGFR-2 dual TK inhibitors. Front Chem.,  2020, 7, 917.
[http://dx.doi.org/10.3389/fchem.2019.00917] [PMID: 32039146] 
[60] 
Karrouchi, K.; Radi, S.; Ramli, Y.; Taoufik, J.; Mabkhot, Y.N.; Al-Aizari, F.A.; Ansar, M. Synthesis and pharmacological activities of pyrazole derivatives: A review. Molecules,  2018, 23(1), 134.
[http://dx.doi.org/10.3390/molecules23010134] [PMID: 29329257] 
[61] 
Menichincheri, M.; Ardini, E.; Magnaghi, P.; Avanzi, N.; Banfi, P.; Bossi, R.; Buffa, L.; Canevari, G.; Ceriani, L.; Colombo, M.; Corti, L.; Donati, D.; Fasolini, M.; Felder, E.; Fiorelli, C.; Fiorentini, F.; Galvani, A.; Isacchi, A.; Borgia, A.L.; Marchionni, C.; Nesi, M.; Orrenius, C.; Panzeri, A.; Pesenti, E.; Rusconi, L.; Saccardo, M.B.; Vanotti, E.; Perrone, E.; Orsini, P. Discovery of entrectinib: A new 3-aminoindazole as a potent Anaplastic Lymphoma Kinase (ALK), c-ros oncogene 1 kinase (ROS1), and Pan-tropomyosin receptor kinases (Pan-TRKs) inhibitor. J. Med. Chem.,  2016, 59(7), 3392-3408.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00064] [PMID: 27003761] 
[62] 
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] 
[63] 
Sharma, G.V.M.; Ramesh, A.; Singh, A.; Srikanth, G.; Jayaram, V.; Duscharla, D.; Jun, J.H.; Ummanni, R.; Malhotra, S.V. Imidazole derivatives show anticancer potential by inducing apoptosis and cellular senescence. MedChemComm,  2014, 5(11), 1751-1760.
[http://dx.doi.org/10.1039/C4MD00277F] 
[64] 
Shaker, S.A.; Marzouk, M.I. Utilization of cyanoacetohydrazide and oxadiazolyl acetonitrile in the synthesis of some new cytotoxic heterocyclic compounds.,  2016, 21(2), 155-179.
[65] 
Abidi, A. Hedgehog signaling pathway: A novel target for cancer therapy: Vismodegib, a promising therapeutic option in treatment of basal cell carcinomas. Indian J. Pharmacol.,  2014, 46(1), 3-12.
[http://dx.doi.org/10.4103/0253-7613.124884] [PMID: 24550577] 
[66] 
Daher, S.; Massarwa, M.; Benson, A.A.; Khoury, T. Current and future treatment of hepatocellular carcinoma: an updated comprehensive review. J. Clin. Transl. Hepatol.,  2018, 6(1), 69-78.
[67] 
Gauthier, A.; Ho, M. Role of sorafenib in the treatment of advanced hepatocellular carcinoma: An update. Hepatol. Res.,  2013, 43(2), 147-154.
[http://dx.doi.org/10.1111/j.1872-034X.2012.01113.x] [PMID: 23145926] 
[68] 
Jain, S.; Chandra, V.; Jain, P.K.; Pathak, K.; Pathak, D.; Vaidya, A. Comprehensive review on current developments of quinoline-based anticancer agents. Arab. J. Chem.,  2019, 12(8), 4920-4946.
[http://dx.doi.org/10.1016/j.arabjc.2016.10.009] 
[69] 
Hamdy, R.; Elseginy, S.A.; Ziedan, N.I.; Jones, A.T.; Westwell, A.D. New quinoline-based heterocycles as anticancer agents targeting bcl-2. Molecules,  2019, 24(7), 1274.
[http://dx.doi.org/10.3390/molecules24071274] [PMID: 30986908] 
[70] 
Wang, Q.; Zorn, J.A.; Kuriyan, J. A structural atlas of kinases inhibited by clinically approved drugs. Methods Enzymol.,  2014, 548, 23-67.
[http://dx.doi.org/10.1016/B978-0-12-397918-6.00002-1] [PMID: 25399641] 
[71] 
Capozzi, M.; De Divitiis, C.; Ottaiano, A.; von Arx, C.; Scala, S.; Tatangelo, F.; Delrio, P.; Tafuto, S. Lenvatinib, a molecule with versatile application: From preclinical evidence to future development in anti-cancer treatment. Cancer Manag. Res.,  2019, 11, 3847-3860.
[http://dx.doi.org/10.2147/CMAR.S188316] [PMID: 31118801] 
[72] 
Hao, Z.; Wang, P. Lenvatinib in management of solid tumors. Oncologist,  2020, 25(2), e302-e310.
[http://dx.doi.org/10.1634/theoncologist.2019-0407] [PMID: 32043789] 
[73] 
Deiters, A.; Martin, S.F. Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis. Chem. Rev.,  2004, 104(5), 2199-2238.
[http://dx.doi.org/10.1021/cr0200872] [PMID: 15137789] 
[74] 
Singh, P.K.; Silakari, O. Current status of O-heterocycles: A synthetic and medicinal overview. ChemMedChem,  2018, 13(11), 1071-1087.
[http://dx.doi.org/10.1002/cmdc.201800119] [PMID: 29603634] 
[75] 
Rowinsky, E.K.; Eisenhauer, E.A.; Chaudhry, V.; Arbuck, S.G.; Donehower, R.C. Clinical toxicities encountered with paclitaxel (Taxol). Semin. Oncol.,  1993, 20(4)(Suppl. 3), 1-15.
[PMID: 8102012] 
[76] 
Kampan, N.C.; Madondo, M.T.; McNally, O.M.; Quinn, M.; Plebanski, M. Paclitaxel and its evolving role in the management of ovarian cancer. BioMed Res. Int.,  2015, 2015413076
[http://dx.doi.org/10.1155/2015/413076] [PMID: 26137480] 
[77] 
Whitaker, R.H.; Placzek, W.J. Regulating the Bcl2 family to improve sensitivity to microtubule targeting agents. Cells,  2019, 8(4), 346.
[http://dx.doi.org/10.3390/cells8040346] [PMID: 31013740] 
[78] 
Kaur, P.; Arora, R.; Gill, N. Review on oxygen heterocycles. Indo. Am. J. Pharm. Res.,  2013, 3, 9067-9084.
[79] 
Madda, J.; Venkatesham, A.; Naveen Kumar, B.; Nagaiah, K.; Sujitha, P.; Ganesh Kumar, C.; Rao, T.P.; Jagadeesh Babu, N. Synthesis of novel chromeno-annulated cis-fused pyrano[3,4-c]benzopyran and naphtho pyran derivatives via domino aldol-type/hetero diels-alder reaction and their cytotoxicity evaluation. Bioorg. Med. Chem. Lett.,  2014, 24(18), 4428-4434.
[http://dx.doi.org/10.1016/j.bmcl.2014.08.005] [PMID: 25172420] 
[80] 
Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids,  2015, 98, 80-91.
[http://dx.doi.org/10.1016/j.steroids.2015.03.001] [PMID: 25759119] 
[81] 
Kumar, D.; Sharma, P.; Singh, H.; Nepali, K.; Gupta, G.K.; Jain, S.K.; Ntie-Kang, F. The value of pyrans as anticancer scaffolds in medicinal chemistry. RSC Advances,  2017, 7(59), 36977-36999.
[http://dx.doi.org/10.1039/C7RA05441F] 
[82] 
Liu, N.; Li, X.; Huang, H.; Zhao, C.; Liao, S.; Yang, C.; Liu, S.; Song, W.; Lu, X.; Lan, X.; Chen, X.; Yi, S.; Xu, L.; Jiang, L.; Zhao, C.; Dong, X.; Zhou, P.; Li, S.; Wang, S.; Shi, X.; Dou, P.Q.; Wang, X.; Liu, J. Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth. Oncotarget,  2014, 5(14), 5453-5471.
[http://dx.doi.org/10.18632/oncotarget.2113] [PMID: 24977961] 
[83] 
Park, S.H.; Lee, J.H.; Berek, J.S.; Hu, M.C. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int. J. Oncol.,  2014, 45(4), 1691-1698.
[http://dx.doi.org/10.3892/ijo.2014.2579] [PMID: 25096914] 
[84] 
Pingaew, R.; Saekee, A.; Mandi, P.; Nantasenamat, C.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents. Eur. J. Med. Chem.,  2014, 85, 65-76.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.087] [PMID: 25078311] 
[85] 
Wu, L.; Wang, G.; Liu, S.; Wei, J.; Zhang, S.; Li, M.; Zhou, G.; Wang, L. Synthesis and biological evaluation of matrine derivatives containing benzo-α-pyrone structure as potent anti-lung cancer agents. Sci. Rep.,  2016, 6(1), 35918.
[http://dx.doi.org/10.1038/srep35918] [PMID: 27786281] 
[86] 
Chen, L.W.; Wang, Z.F.; Zhu, B.; Man, R.J.; Liu, Y.D.; Zhang, Y.H.; Wang, B.Z.; Wang, Z.C.; Zhu, H.L. synthesis and biological evaluation of novel benzo-α-pyrone containing piperazine derivatives as potential BRAFV600E inhibitors. Bioorg. Med. Chem. Lett.,  2016, 26(20), 4983-4991.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.003] [PMID: 27634195] 
[87] 
El-Ansary, S.L.; Abdel Rahman, D.E.; Abdel Ghany, L.M.A. Synthesis and anticancer evaluation of some new 3-benzyl-4,8-dimethylbenzopyrone derivatives. Open Med. Chem. J.,  2017, 11(1), 81-91.
[http://dx.doi.org/10.2174/1874104501711010081] [PMID: 29151985] 
[88] 
Marshall, M.E.; Ryles, M.; Butler, K.; Weiss, L. Treatment of advanced renal cell carcinoma (RCC) with coumarin and cimetidine: Longterm follow-up of patients treated on a phase I trial. J. Cancer Res. Clin. Oncol.,  1994, 120, 535-538.
[89] 
Weber, U.S.; Steffen, B.; Siegers, C.P. Antitumor-activities of coumarin, 7-hydroxy-coumarin and its glucuronide in several human tumor cell lines. Res. Commun. Mol. Pathol. Pharmacol.,  1998, 99(2), 193-206.
[PMID: 9583093] 
[90] 
Budzisz, E.; Brzezinska, E.; Krajewska, U.; Rozalski, M. Cytotoxic effects, alkylating properties and molecular modelling of coumarin derivatives and their phosphonic analogues. Eur. J. Med. Chem.,  2003, 38(6), 597-603.
[http://dx.doi.org/10.1016/S0223-5234(03)00086-2] [PMID: 12832131] 
[91] 
Stanchev, S.; Momekov, G.; Jensen, F.; Manolov, I. Synthesis, computational study and cytotoxic activity of new 4-hydroxycoumarin derivatives. Eur. J. Med. Chem.,  2008, 43(4), 694-706.
[http://dx.doi.org/10.1016/j.ejmech.2007.05.005] [PMID: 17614164] 
[92] 
Pan, L.; Chai, H.; Kinghorn, A.D. The continuing search for antitumor agents from higher plants. Phytochem. Lett.,  2010, 3(1), 1-8.
[http://dx.doi.org/10.1016/j.phytol.2009.11.005] [PMID: 20228943] 
[93] 
vianna, D.R.; Hamerski, L.; Figueiró, F.; Bernardi, A.; Visentin, L.C.; Pires, E.N.; Teixeira, H.F.; Salbego, C.G.; Eifler-Lima, V.L.; Battastini, A.M.; von Poser, G.L.; Pinto, A.C. Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species. Eur. J. Med. Chem.,  2012, 57, 268-274.
[http://dx.doi.org/10.1016/j.ejmech.2012.09.007] [PMID: 23069682] 
[94] 
Pádua, D.; Rocha, E.; Gargiulo, D.; Ramos, A.A. Bioactive compounds from brown seaweeds: Phloroglucinol, fucoxanthin and fucoidan as promising therapeutic agents against breast cancer. Phytochem. Lett.,  2015, 14, 91-98.
[http://dx.doi.org/10.1016/j.phytol.2015.09.007] 
[95] 
Borik, R.M.; Fawzy, N.M.; Abu-Bakr, S.M.; Aly, M.S. Design, synthesis, anticancer evaluation and docking studies of novel heterocyclic derivatives obtained via reactions involving curcumin. Molecules,  2018, 23(6), 1398.
[http://dx.doi.org/10.3390/molecules23061398] [PMID: 29890691] 
[96] 
Fang, H.; Ji, H.; Furanocoumarin, A. A novel anticancer agent on human lung cancer A549 cells from fructus Liquidambaris. Anticancer. Agents Med. Chem.,  2019, 19(17), 2091-2096.
[http://dx.doi.org/10.2174/1871520619666191010102526] [PMID: 31782355] 
[97] 
Küpeli Akkol, E.; Genç, Y.; Karpuz, B.; Sobarzo-Sánchez, E.; Capasso, R. Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers (Basel),  2020, 12(7), 1959-1983.
[http://dx.doi.org/10.3390/cancers12071959] [PMID: 32707666] 
[98] 
Majnooni, M.B.; Fakhri, S.; Shokoohinia, Y.; Mojarrab, M.; Kazemi-Afrakoti, S.; Farzaei, M.H. Isofraxidin: Synthesis, biosynthesis, isolation, pharmacokinetic and pharmacological properties. Molecules,  2020, 25(9), 2040.
[http://dx.doi.org/10.3390/molecules25092040] [PMID: 32349420] 
[99] 
Pinto, M.M.M.; Palmeira, A.; Fernandes, C.; Resende, D.I.S.P.; Sousa, E.; Cidade, H.; Tiritan, M.E.; Correia-da-Silva, M.; Cravo, S. From natural products to new synthetic small molecules: A journey through the world of xanthones. Molecules,  2021, 26(2), 431.
[http://dx.doi.org/10.3390/molecules26020431] [PMID: 33467544] 
[100] 
Klein-Júnior, L.C.; Campos, A.; Niero, R.; Corrêa, R.; Vander Heyden, Y.; Filho, V.C. Xanthones and cancer: From natural sources to mechanisms of action. Chem. Biodivers.,  2020, 17(2)e1900499
[http://dx.doi.org/10.1002/cbdv.201900499] [PMID: 31794156] 
[101] 
Lin, C.N.; Liou, S.J.; Lee, T.H.; Chuang, Y.C.; Won, S.J. Xanthone derivatives as potential anti-cancer drugs. J. Pharm. Pharmacol.,  1996, 48(5), 539-544.
[http://dx.doi.org/10.1111/j.2042-7158.1996.tb05970.x] [PMID: 8799883] 
[102] 
Pouli, N.; Marakos, P. Fused xanthone derivatives as antiproliferative agents. Anticancer. Agents Med. Chem.,  2009, 9(1), 77-98.
[http://dx.doi.org/10.2174/187152009787047699] [PMID: 19149484] 
[103] 
Lim, C.K.; Tho, L.Y.; Lim, Y.M.; Shah, S.A.A.; Weber, J.F.F. Synthesis of 1,3,6-trioxygenated prenylated xanthone derivatives as potential antitumor agents. Lett. Org. Chem.,  2012, 9(8), 549-555.
[http://dx.doi.org/10.2174/157017812802850230] 
[104] 
Liu, J.; Zhou, F.; Zhang, L.; Wang, H.; Zhang, J.; Zhang, C.; Jiang, Z.; Li, Y.; Liu, Z.; Chen, H. DMXAA-pyranoxanthone hybrids enhance inhibition activities against human cancer cells with multi-target functions. Eur. J. Med. Chem.,  2018, 143, 1768-1778.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.074] [PMID: 29129511] 
[105] 
Miladiyah, I.; Jumina, J.; Haryana, S.M.; Mustofa, M. Biological activity, quantitative structure-activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs. Drug Des. Devel. Ther.,  2018, 12, 149-158.
[http://dx.doi.org/10.2147/DDDT.S149973] [PMID: 29391779] 
[106] 
Manikandan, A.; Sivakumar, A.; Nigam, P.S.; Napoleon, A.A. Anticancer effects of novel tetrahydro-dimethyl-xanthene-diones. Anticancer. Agents Med. Chem.,  2020, 20(7), 909-916.
[http://dx.doi.org/10.2174/1871520620666200318094138] [PMID: 32188389] 
[107] 
Ibrahim, M.Y.; Hashim, N.M.; Mariod, A.A.; Mohan, S.; Abdulla, M.A.; Abdelwahab, S.I.; Arbab, I.A. α-mangostin from Garcinia mangostana Linn: An updated review of its pharmacological properties. Arab. J. Chem.,  2016, 9(3), 317-329.
[http://dx.doi.org/10.1016/j.arabjc.2014.02.011] 
[108] 
Zhang, K.J.; Gu, Q.L.; Yang, K.; Ming, X.J.; Wang, J.X. Anticarcinogenic effects of α-mangostin: A review. Planta Med.,  2017, 83(3-04), 188-202.
[109] 
Abdel-Wahab, B.F.; Shaaban, S.; El-Hiti, G.A. Synthesis of sulfur-containing heterocycles via ring enlargement. Mol. Divers.,  2018, 22(2), 517-542.
[http://dx.doi.org/10.1007/s11030-017-9810-3] [PMID: 29388031] 
[110] 
Pathania, S.; Narang, R.K.; Rawal, R.K. Role of sulphur-heterocycles in medicinal chemistry: An update. Eur. J. Med. Chem.,  2019, 180, 486-508.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.043] [PMID: 31330449] 
[111] 
Schutte, L.; Teranishi, R. Precursors of sulfur-containing flavor compounds. Crit. Rev. Food Sci. Nutr.,  1974, 4(4), 457-505.
[112] 
Feng, M.; Tang, B.; Liang, S.H.; Jiang, X. Sulfur containing scaffolds in drugs: Synthesis and application in medicinal chemistry. Curr. Top. Med. Chem.,  2016, 16(11), 1200-1216.
[http://dx.doi.org/10.2174/1568026615666150915111741] [PMID: 26369815] 
[113] 
Nayak, K.R.; Cavendish, J.J. Risk reduction with clopidogrel in the management of peripheral arterial disease. Vasc. Health Risk Manag.,  2007, 3(3), 289-297.
[PMID: 17703636] 
[114] 
Rawal, R.K.; Murugesan, V.; Katti, S.B. Structure-activity relationship studies on clinically relevant HIV-1 NNRTIs. Curr. Med. Chem.,  2012, 19(31), 5364-5380.
[http://dx.doi.org/10.2174/092986712803833326] [PMID: 22998569] 
[115] 
Kim, D.E.; Kim, Y.; Cho, D.H.; Jeong, S.Y.; Kim, S.B.; Suh, N.; Lee, J.S.; Choi, E.K.; Koh, J.Y.; Hwang, J.J.; Kim, C.S. Raloxifene induces autophagy-dependent cell death in breast cancer cells via the activation of AMP-activated protein kinase. Mol. Cell,  2015, 38(2), 138-144.
[http://dx.doi.org/10.14348/molcells.2015.2193] [PMID: 25537862] 
[116] 
Herdeiro, M.T.; Soares, S.; Silva, T.; Roque, F.; Figueiras, A. Impact of rosiglitazone safety alerts on oral antidiabetic sales trends: A countrywide study in Portugal. Fundam. Clin. Pharmacol.,  2016, 30(5), 440-449.
[http://dx.doi.org/10.1111/fcp.12207] [PMID: 27259384] 
[117] 
Séïde, M.; Marion, M.; Mateescu, M.A.; Averill-Bates, D.A. The fungicide thiabendazole causes apoptosis in rat hepatocytes. Toxicol. In Vitro,  2016, 32, 232-239.
[http://dx.doi.org/10.1016/j.tiv.2015.12.018] [PMID: 26748015] 
[118] 
Aljamali, N.M. Review in cyclic compounds with hetero atoms. Int. J. Curr. Res. Chem. Pharma Sci.,  2014, 1(9), 88-120.
[119] 
Poroikov, V.V.; Gloriozova, T.A.; Dembitsky, V.M. Natural occurring thiirane containing compounds: Origin, chemistry, and their pharmacological activities. Pharm. Chem. J.,  2017, 4(5), 107-120.
[120] 
Zapico, J.M.; Serra, P.; García-Sanmartín, J.; Filipiak, K.; Carbajo, R.J.; Schott, A.K.; Pineda-Lucena, A.; Martínez, A.; Martín-Santamaría, S.; de Pascual-Teresa, B.; Ramos, A. Potent “clicked” MMP2 inhibitors: Synthesis, molecular modeling and biological exploration. Org. Biomol. Chem.,  2011, 9(12), 4587-4599.
[http://dx.doi.org/10.1039/c0ob00852d] [PMID: 21552627] 
[121] 
Fabre, B.; Filipiak, K.; Coderch, C.; Zapico, J.M.; Carbajo, R.J.; Schott, A.K.; Pineda-Lucena, A.; Pascual Teresa, B.; Ramos, A. New clicked thiirane derivatives as gelatinase inhibitors: The relevance of the P10 segment. RSC Advances,  2014, 4(34), 17726-17735.
[http://dx.doi.org/10.1039/c3ra46402d] 
[122] 
Tian, Y.; Wei, X.; Xu, H. Photoactivated insecticidal thiophene derivatives from Xanthopappus subacaulis. J. Nat. Prod.,  2006, 69(8), 1241-1244.
[http://dx.doi.org/10.1021/np060209b] [PMID: 16933888] 
[123] 
Mishra, R.; Sharma, P.K. A review on synthesis and medicinal importance of thiophene. Int. J. Eng. Sci.,  2015, 1(1), 46-59.
[124] 
Shah, R.; Verma, P.K. Therapeutic importance of synthetic thiophene. Chem. Cent. J.,  2018, 12(1), 137-158.
[http://dx.doi.org/10.1186/s13065-018-0511-5] [PMID: 30564984] 
[125] 
Rodrigues, K.A.F.; Dias, C.N.S.; Néris, P.L.N.; Rocha, J.C.; Scotti, M.T.; Scotti, L.; Mascarenhas, S.R.; Veras, R.C.; de Medeiros, I.A.; Keesen, T.S.; de Oliveira, T.B.; de Lima, M.C.; Balliano, T.L.; de Aquino, T.M.; de Moura, R.O.; Mendonça, Junior, F.J.; de Oliveira, M.R. 2-Amino-thiophene derivatives present antileishmanial activity mediated by apoptosis and immunomodulation in vitro. Eur. J. Med. Chem.,  2015, 106, 1-14.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.011] [PMID: 26513640] 
[126] 
Hafez, H.N.; Alsalamah, S.A.; El-Gazzar, A.B.A. Synthesis of thiophene and N-substituted thieno[3,2-d] pyrimidine derivatives as potent antitumor and antibacterial agents. Acta Pharm.,  2017, 67(3), 275-292.
[http://dx.doi.org/10.1515/acph-2017-0028] [PMID: 28858838] 
[127] 
Romagnoli, R.; Kimatrai Salvador, M.; Schiaffino Ortega, S.; Baraldi, P.G.; Oliva, P.; Baraldi, S.; Lopez-Cara, L.C.; Brancale, A.; Ferla, S.; Hamel, E.; Balzarini, J.; Liekens, S.; Mattiuzzo, E.; Basso, G.; Viola, G. 2-Alkoxycarbonyl-3-arylamino-5-substituted thiophenes as a novel class of antimicrotubule agents: Design, synthesis, cell growth and tubulin polymerization inhibition. Eur. J. Med. Chem.,  2018, 143, 683-698.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.096] [PMID: 29220790] 
[128] 
Rey, J.R.; Cervino, E.V.; Rentero, M.L.; Crespo, E.C.; Álvaro, A.O.; Casillas, M. Raloxifene: Mechanism of action, effects on bone tissue, and applicability in clinical traumatology practice. Open Orthop. J.,  2009, 3(1), 14-21.
[http://dx.doi.org/10.2174/1874325000903010014] [PMID: 19516920] 
[129] 
Palchykov, V.A.; Chabanenko, R.M.; Konshin, V.V.; Dotsenko, V.V.; Krivokolysko, S.G.; Chigorina, E.A.; Horak, Y.I.; Lytvyn, R.Z.; Vakhula, A.A.; Obushak, M.D.; Mazepa, A.V. Dihydro-2 H-thiopyran-3 (4 H)-one-1,1-dioxideea versatile building block for the synthesis of new thiopyran-based heterocyclic systems. New J. Chem.,  2018, 42(2), 1403-1412.
[http://dx.doi.org/10.1039/C7NJ03846A] 
[130] 
Wang, S.; Jiang, Y.; Wu, S.; Dong, G.; Miao, Z.; Zhang, W.; Sheng, C. Meeting organocatalysis with drug discovery: asymmetric synthesis of 3,3′-spirooxindoles fused with tetrahydrothiopyrans as novel p53-MDM2 inhibitors. Org. Lett.,  2016, 18(5), 1028-1031.
[http://dx.doi.org/10.1021/acs.orglett.6b00155] [PMID: 26883465] 
[131] 
Ji, C.; Wang, S.; Chen, S.; He, S.; Jiang, Y.; Miao, Z.; Li, J.; Sheng, C. Design, synthesis and biological evaluation of novel antitumor spirotetrahydrothiopyran-oxindole derivatives as potent p53-MDM2 inhibitors. Bioorg. Med. Chem.,  2017, 25(20), 5268-5277.
[http://dx.doi.org/10.1016/j.bmc.2017.07.049] [PMID: 28797774] 
[132] 
Lozynskyi, A.; Golota, S.; Zimenkovsky, B.; Atamanyuk, D.; Gzella, A.; Lesyk, R. Synthesis, anticancer and antiviral activities of novel thiopyrano [2,3-d]thiazole-6-carbaldehydes. Phosphorus Sulfur Silicon Relat. Elem.,  2016, 191(9), 1245-1249.
[http://dx.doi.org/10.1080/10426507.2016.1166108] 
[133] 
Zheng, X.; Liu, W.; Zhang, D. Recent advances in the synthesis of oxazole-based molecules via van leusen oxazole synthesis. Molecules,  2020, 25(7), 1594.
[http://dx.doi.org/10.3390/molecules25071594] [PMID: 32244317] 
[134] 
Chiacchio, M.A.; Lanza, G.; Chiacchio, U.; Giofrè, S.V.; Romeo, R.; Iannazzo, D.; Legnani, L. Oxazole-based compounds as anticancer agents. Curr. Med. Chem.,  2019, 26(41), 7337-7371.
[http://dx.doi.org/10.2174/0929867326666181203130402] [PMID: 30501590] 
[135] 
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] 
[136] 
Akhtar, M.J.; Siddiqui, A.A.; Khan, A.A.; Ali, Z.; Dewangan, R.P.; Pasha, S.; Yar, M.S. Design, synthesis, docking and QSAR study of substituted benzimidazole linked oxadiazole as cytotoxic agents, EGFR and erbB2 receptor inhibitors. Eur. J. Med. Chem.,  2017, 126, 853-869.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.014] [PMID: 27987485] 
[137] 
Glomb, T.; Szymankiewicz, K.; Świątek, P. Anti-cancer activity of derivatives of 1,3,4-oxadiazole. Molecules,  2018, 23(12), 3361.
[http://dx.doi.org/10.3390/molecules23123361] [PMID: 30567416] 
[138] 
Abdellatif, K.R.A.; Fadaly, W.A.A.; Kamel, G.M.; Elshaier, Y.A.M.; El-Magd, M.A. Design, synthesis, modeling studies and biological evaluation of thiazolidine derivatives containing pyrazole core as potential anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective inhibitors. Bioorg. Chem.,  2019, 82, 86-99.
[http://dx.doi.org/10.1016/j.bioorg.2018.09.034] [PMID: 30278282] 
[139] 
Kaur Manjal, S.; Kaur, R.; Bhatia, R.; Kumar, K.; Singh, V.; Shankar, R.; Kaur, R.; Rawal, R.K. Synthetic and medicinal perspective of thiazolidinones: A review. Bioorg. Chem.,  2017, 75, 406-423.
[http://dx.doi.org/10.1016/j.bioorg.2017.10.014] [PMID: 29102723] 
[140] 
Asati, V.; Bharti, S.K. Design, synthesis and molecular modeling studies of novel thiazolidine-2, 4-dione derivatives as potential anti-cancer agents. J. Mol. Struct.,  2018, 1154, 406-417.
[http://dx.doi.org/10.1016/j.molstruc.2017.10.077] 
[141] 
Kaberdin, R.V.; Potkin, V.I. Isothiazoles (1, 2-thiazoles): Synthesis, properties and applications. Russ. Chem. Rev.,  2002, 71(8), 673-694.
[http://dx.doi.org/10.1070/RC2002v071n08ABEH000738] 
[142] 
Clerici, F.; Contini, A.; Corsini, A.; Ferri, N.; Grzesiak, S.; Pellegrino, S.; Sala, A.; Yokoyama, K. Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides. Eur. J. Med. Chem.,  2006, 41(5), 675-682.
[http://dx.doi.org/10.1016/j.ejmech.2006.01.009] [PMID: 16540206] 
[143] 
Ono, K.; Banno, H.; Okaniwa, M.; Hirayama, T.; Iwamura, N.; Hikichi, Y.; Murai, S.; Hasegawa, M.; Hasegawa, Y.; Yonemori, K. Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4, 5-dihydrothieno [3ʹ, 4ʹ: 3, 4] benzo [1, 2-d] isothiazole derivatives. Bioorg. Med. Chem.,  2017, 25, 2336-2350.
[http://dx.doi.org/10.1016/j.bmc.2017.02.038] [PMID: 28302507] 
[144] 
Farghaly, T.A.; El-Metwaly, N.; Al-Soliemy, A.M.; Katouah, H.A.; Muhammad, Z.A.; Sabour, R. Synthesis, molecular docking and antitumor activity of new dithiazoles. Polycycl. Aromat. Compd.,  2019, 2019, 1-17.
[145] 
Cui, X.; Fang, X.; Zhao, H.; Li, Z.; Ren, H. Fabrication of thiazole derivatives functionalized graphene decorated with fluorine, chlorine and iodine@ SnO2 nanoparticles for highly sensitive detection of heavy metal ions. Colloids Surf. A Physicochem. Eng. Asp.,  2018, 546, 153-162.
[http://dx.doi.org/10.1016/j.colsurfa.2018.03.004] 
[146] 
Ayati, A.; Esmaeili, R.; Moghimi, S.; Oghabi Bakhshaiesh, T.; Eslami-S, Z.; Majidzadeh-A, K.; Safavi, M.; Emami, S.; Foroumadi, A. Synthesis and biological evaluation of 4-amino-5-cinnamoylthiazoles as chalcone-like anticancer agents. Eur. J. Med. Chem.,  2018, 145, 404-412.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.015] [PMID: 29335206] 
[147] 
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] 
[148] 
Patel, S.; Patle, R.; Parameswaran, P.; Jain, A.; Shard, A. Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents. Eur. J. Pharm. Sci.,  2019, 134, 20-30.
[http://dx.doi.org/10.1016/j.ejps.2019.04.005] [PMID: 30965082] 
[149] 
Bhullar, K.S.; Lagarón, N.O.; McGowan, E.M.; Parmar, I.; Jha, A.; Hubbard, B.P.; Rupasinghe, H.P.V. Kinase-targeted cancer therapies: Progress, challenges and future directions. Mol. Cancer,  2018, 17(1), 48.
[http://dx.doi.org/10.1186/s12943-018-0804-2] [PMID: 29455673] 
[150] 
Holderfield, M.; Deuker, M.M.; McCormick, F.; McMahon, M. Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat. Rev. Cancer,  2014, 14(7), 455-467.
[http://dx.doi.org/10.1038/nrc3760] [PMID: 24957944] 
[151] 
Scott, K.A.; Njardarson, J.T. Analysis of US-FDA approved drugs containing sulfur atoms. Top. Curr. Chem. (Cham),  2018, 376(1), 5.
[http://dx.doi.org/10.1007/s41061-018-0184-5] [PMID: 29356979] 
[152] 
El-Bayouki, K.A. Synthesis, reactions, and biological activity of 1,4- thiazepines and their fused aryl and heteroaryl derivatives: A review. J. Sulfur Chem.,  2011, 32(6), 623-690.
[http://dx.doi.org/10.1080/17415993.2011.607165] 
[153] 
Kelgokmen, Y.; Zora, M. Synthesis of 1,4-thiazepines. J. Org. Chem.,  2018, 83(15), 8376-8389.
[http://dx.doi.org/10.1021/acs.joc.8b01029] [PMID: 29936840] 
[154] 
Wu, L.; Yang, X.; Peng, Q.; Sun, G. Synthesis and anti-proliferative activity evaluation of novel benzo[d][1,3] dioxoles-fused 1,4-thiazepines. Eur. J. Med. Chem.,  2017, 127, 599-605.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.021] [PMID: 28119200] 
[155] 
Xiang, J.; Zhang, Z.; Mu, Y.; Xu, X.; Guo, S.; Liu, Y.; Russo, D.P.; Zhu, H.; Yan, B.; Bai, X. Discovery of novel tricyclic thiazepine derivatives as anti-drug-resistant cancer agents by combining diversity-oriented synthesis and converging screening approach. ACS Comb. Sci.,  2016, 18(5), 230-235.
[http://dx.doi.org/10.1021/acscombsci.6b00010] [PMID: 27082930] 
[156] 
Lazo, J.S.; Sharlow, E.R. Drugging undruggable molecular cancer targets. Annu. Rev. Pharmacol. Toxicol.,  2016, 56(1), 23-40.
[http://dx.doi.org/10.1146/annurev-pharmtox-010715-103440] [PMID: 26527069] 
[157] 
Lu, P.; Bevan, D.R.; Leber, A.; Hontecillas, R.; Tubau-Juni, N.; Bassaganya-Riera, J. Computer-aided drug discovery. Accelerated Path to Cures; Bassaganya-Riera, J., Ed.; Springer: Cham, 2018, pp. 7-24.
[http://dx.doi.org/10.1007/978-3-319-73238-1_2] 
[158] 
Cui, W.; Aouidate, A.; Wang, S.; Yu, Q.; Li, Y.; Yuan, S. Discovering anti-cancer drugs via computational methods. Front. Pharmacol.,  2020, 11, 733.
[http://dx.doi.org/10.3389/fphar.2020.00733] [PMID: 32508653] 
[159] 
Takarabe, M.; Kotera, M.; Nishimura, Y.; Goto, S.; Yamanishi, Y. Drug target prediction using adverse event report systems: A pharmacogenomic approach. Bioinformatics,  2012, 28(18), i611-i618.
[http://dx.doi.org/10.1093/bioinformatics/bts413] [PMID: 22962489] 
[160] 
Yildirim, M.A.; Goh, K.I.; Cusick, M.E.; Barabási, A.L.; Vidal, M. Drug-target network. Nat. Biotechnol.,  2007, 25(10), 1119-1126.
[http://dx.doi.org/10.1038/nbt1338] [PMID: 17921997] 
[161] 
Li, X.; Chen, H.C. Recommendation as link prediction in bipartite graphs: A graph kernel-based machine learning approach. Decis. Support Syst.,  2013, 54(2), 880-890.
[http://dx.doi.org/10.1016/j.dss.2012.09.019] 
[162] 
Srivastava, N.; Hinton, G.; Krizhevsky, A.; Sutskever, I.; Salakhutdinov, R. Dropout: A simple way to prevent neural networks from overfitting. J. Mach. Learn. Res.,  2014, 15(56), 1929-1958.
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DOI https://dx.doi.org/10.2174/1871520622666220404082648	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992
Anti-Cancer Agents in Medicinal Chemistry

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