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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Structural Insights into N-heterocyclic Moieties as an Anticancer Agent against Hepatocellular Carcinoma: An Exhaustive Perspective

Author(s): Nikhil Kumar Chourasiya, Firdous Fatima, Mitali Mishra, Shivam Kori, Ratnesh Das, Varsha Kashaw, Arun K. Iyer and Sushil Kumar Kashaw*

Volume 23, Issue 19, 2023

Published on: 15 June, 2023

Page: [1871 - 1892] Pages: 22

DOI: 10.2174/1389557523666230508160924

Price: $65

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Abstract

Hepatocellular carcinoma (HCC) is rapidly spreading around the world with a high mortality rate. In the low- and middle-income nations most impacted by HCV and HBV infections, HCC places a significant strain on the healthcare system and leaches productive capability. An extensive study on HCC to create novel therapeutic approaches was motivated by the lack of adequate preventive or curative therapy methods. Several medications have been put forward and some drug molecules are under investigation by the Food and Drug Administration (FDA) for the treatment of HCC. However, these therapeutic choices fall short of the ideal due to toxicity and the rapid rise in drug resistance which decreases the efficacy of these therapeutics and leads to the severity of hepatocellular carcinoma. Therefore, concerning these problems, there is a critical need for novel systemic combination therapies as well as novel molecular entities that target various signalling pathways, reducing the likelihood that cancer cells may develop treatment resistance. In this review, we discuss the conclusions of several studies suggesting that the N-heterocyclic ring system is a key structural component of many synthetic drugs with a diverse range of biological activities. Following nuclei, such as pyridazine, pyridine, and pyrimidines, along with benzimidazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, quinolines, and quinazolines, have been included to provide a general overview of the link between structure and activity between heterocyclics and their derivatives against hepatocellular carcinoma. A comprehensive investigation of the structure-activity relationship between the series may be done by the direct comparison of anticancer activities with the reference.

Graphical Abstract

[1]
Galle, P.R.; Forner, A.; Llovet, J.M.; Mazzaferro, V.; Piscaglia, F.; Raoul, J-L.; Schirmacher, P.; Vilgrain, V. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J. Hepatol., 2018, 69(1), 182-236.
[PMID: 29628281] [http://dx.doi.org/10.1016/j.jhep.2018.03.019]
[2]
Yang, J.D.; Roberts, L.R. Hepatocellular carcinoma: A global view. Nat. Rev. Gastroenterol. Hepatol., 2010, 7(8), 448-458.
[http://dx.doi.org/10.1038/nrgastro.2010.100] [PMID: 20628345]
[3]
Zhao, J.; Gray, S.G.; Greene, C.M.; Lawless, M.W. Unmasking the pathological and therapeutic potential of histone deacetylases for liver cancer. Expert Rev. Gastroenterol. Hepatol., 2019, 13(3), 247-256.
[http://dx.doi.org/10.1080/17474124.2019.1568870] [PMID: 30791763]
[5]
LaFemina, J.; Switzer, B. Whalen, GF Liver cancer: Hepatocellular carcinoma; Cancer Prev. Early. Detect. Treat. Recover, 2019, pp. 327-343.
[6]
Choi, K.J.; Baik, I.H.; Ye, S.K.; Lee, Y.H. 2015.
[PMID: 26133708]
[7]
Dogan, Z.; Paulini, R.; Rojas Stütz, J.A.; Narayanan, S.; Richert, C. 5′-Tethered stilbene derivatives as fidelity- and affinity-enhancing modulators of DNA duplex stability. J. Am. Chem. Soc., 2004, 126(15), 4762-4763.
[http://dx.doi.org/10.1021/ja0394434] [PMID: 15080664]
[8]
Koulouris, A.; Sagkaris, C.T.; Spyrou, V.; Pappa, E.; Troullinou, A. 2021.
[PMID: 34012929]
[9]
Yang, D.; An, B.; Wei, W.; Tian, L.; Huang, B.; Wang, H. Copper-catalyzed domino synthesis of nitrogen heterocycle-fused benzoimidazole and 1,2,4-benzothiadiazine 1,1-dioxide derivatives. ACS Comb. Sci., 2015, 17(2), 113-119.
[http://dx.doi.org/10.1021/co500125n] [PMID: 25549532]
[10]
Kim, S.; Abou-Alfa, G.K. The role of tyrosine kinase inhibitors in hepatocellular carcinoma. Clin. Adv. Hematol. Oncol., 2014, 12(1), 36-41.
[PMID: 25000314]
[11]
Llovet, J.M.; Sergio, R.; Vincenzo, M. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med., 2008, 359(4), 378-390.
[http://dx.doi.org/10.1056/NEJMoa0708857] [PMID: 18650514]
[12]
Arora, A.; Scholar, E.M. Role of tyrosine kinase inhibitors in cancer therapy. J. Pharmacol. Exp. Ther., 2005, 315(3), 971-979.
[http://dx.doi.org/10.1124/jpet.105.084145] [PMID: 16002463]
[13]
Hartmann, J.; Haap, M.; Kopp, H.G.; Lipp, H.P. Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr. Drug Metab., 2009, 10(5), 470-481.
[http://dx.doi.org/10.2174/138920009788897975] [PMID: 19689244]
[14]
Hojjat-Farsangi, M. Small-molecule inhibitors of the receptor tyrosine kinases: Promising tools for targeted cancer therapies. Int. J. Mol. Sci., 2014, 15(8), 13768-13801.
[http://dx.doi.org/10.3390/ijms150813768] [PMID: 25110867]
[15]
Garuti, L.; Roberti, M.; Bottegoni, G. Non-ATP competitive protein kinase inhibitors. Curr. Med. Chem., 2010, 17(25), 2804-2821.
[http://dx.doi.org/10.2174/092986710791859333] [PMID: 20586715]
[16]
Malumbres, M. Cyclin-dependent kinases. Genome Biol., 2014, 15(6), 122.
[http://dx.doi.org/10.1186/gb4184] [PMID: 25180339]
[17]
Haider, C.; Grubinger, M.; Řezníčková, E.; Weiss, T.S.; Rotheneder, H.; Miklos, W.; Berger, W.; Jorda, R.; Zatloukal, M.; Gucký, T.; Strnad, M.; Kryštof, V.; Mikulits, W. Novel inhibitors of cyclin-dependent kinases combat hepatocellular carcinoma without inducing chemoresistance. Mol. Cancer Ther., 2013, 12(10), 1947-1957.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0263] [PMID: 23939380]
[18]
Bloom, J.; Cross, F.R. Multiple levels of cyclin specificity in cell-cycle control. Nat. Rev. Mol. Cell Biol., 2007, 8(2), 149-160.
[http://dx.doi.org/10.1038/nrm2105] [PMID: 17245415]
[19]
Rossi, A.G.; Sawatzky, D.A.; Walker, A.; Ward, C.; Sheldrake, T.A.; Riley, N.A.; Caldicott, A.; Martinez-Losa, M.; Walker, T.R.; Duffin, R.; Gray, M.; Crescenzi, E.; Martin, M.C.; Brady, H.J.; Savill, J.S.; Dransfield, I.; Haslett, C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat. Med., 2006, 12(9), 1056-1064.
[http://dx.doi.org/10.1038/nm1468] [PMID: 16951685]
[20]
Fornari, F.; Gramantieri, L.; Ferracin, M.; Veronese, A.; Sabbioni, S.; Calin, G.A.; Grazi, G.L.; Giovannini, C.; Croce, C.M.; Bolondi, L.; Negrini, M. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene, 2008, 27(43), 5651-5661.
[http://dx.doi.org/10.1038/onc.2008.178] [PMID: 18521080]
[21]
Senderowicz, A.M. Targeting cell cycle and apoptosis for the treatment of human malignancies. Curr. Opin. Cell Biol., 2004, 16(6), 670-678.
[http://dx.doi.org/10.1016/j.ceb.2004.09.014] [PMID: 15530779]
[22]
Bisteau, X.; Caldez, M.; Kaldis, P. The complex relationship between liver cancer and the cell cycle: A story of multiple regulations. Cancers , 2014, 6(1), 79-111.
[http://dx.doi.org/10.3390/cancers6010079] [PMID: 24419005]
[23]
Malumbres, M.; Harlow, E.; Hunt, T.; Hunter, T.; Lahti, J.M.; Manning, G.; Morgan, D.O.; Tsai, L.H.; Wolgemuth, D.J. Cyclin-dependent kinases: A family portrait. Nat. Cell Biol., 2009, 11(11), 1275-1276.
[http://dx.doi.org/10.1038/ncb1109-1275] [PMID: 19884882]
[24]
Gopinathan, L.; Ratnacaram, C.K.; Kaldis, P. Established and novel Cdk/cyclin complexes regulating the cell cycle and development. Results Probl. Cell Differ., 2011, 53, 365-389.
[http://dx.doi.org/10.1007/978-3-642-19065-0_16] [PMID: 21630153]
[25]
Paiva, C.; Godbersen, J.C.; Soderquist, R.S.; Rowland, T.; Kilmarx, S.; Spurgeon, S.E.; Brown, J.R.; Srinivasa, S.P.; Danilov, A.V. Cyclin-dependent kinase inhibitor P1446A induces apoptosis in a JNK/p38 MAPK-dependent manner in chronic lymphocytic leukemia B-cells. PLoS One, 2015, 10(11), e0143685.
[http://dx.doi.org/10.1371/journal.pone.0143685] [PMID: 26606677]
[26]
Lam, F.; Abbas, A.Y.; Shao, H.; Teo, T.; Adams, J.; Li, P.; Bradshaw, T.D.; Fischer, P.M.; Walsby, E.; Pepper, C.; Chen, Y.; Ding, J.; Wang, S. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget, 2014, 5(17), 7691-7704.
[http://dx.doi.org/10.18632/oncotarget.2296] [PMID: 25277198]
[27]
Albert, T.K.; Rigault, C.; Eickhoff, J.; Baumgart, K.; Antrecht, C.; Klebl, B.; Mittler, G.; Meisterernst, M. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br. J. Pharmacol., 2014, 171(1), 55-68.
[http://dx.doi.org/10.1111/bph.12408] [PMID: 24102143]
[28]
Kitagawa, M.; Kitagawa, K.; Kotake, Y.; Niida, H.; Ohhata, T. Cell cycle regulation by long non-coding RNAs. Cell. Mol. Life Sci., 2013, 70(24), 4785-4794.
[http://dx.doi.org/10.1007/s00018-013-1423-0] [PMID: 23880895]
[29]
Liu, X.; Shi, S.; Lam, F.; Pepper, C.; Fischer, P.M.; Wang, S. CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol. Int. J. Cancer, 2012, 130(5), 1216-1226.
[http://dx.doi.org/10.1002/ijc.26127] [PMID: 21484792]
[30]
Liu, X.; Lam, F.; Shi, S.; Fischer, P.M.; Wang, S. In vitro antitumor mechanism of a novel cyclin-dependent kinase inhibitor CDKI-83. Invest. New Drugs, 2012, 30(3), 889-897.
[http://dx.doi.org/10.1007/s10637-011-9641-5] [PMID: 21331744]
[31]
Johnson, N.; Bentley, J.; Wang, L-Z.; Newell, D.R.; Robson, C.N.; Shapiro, G.I.; Curtin, N.J. Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in anti-estrogen-sensitive and resistant breast cancer cells. Br. J. Cancer, 2010, 102(2), 342-350.
[http://dx.doi.org/10.1038/sj.bjc.6605479] [PMID: 20010939]
[32]
Albanese, C.; Alzani, R.; Amboldi, N.; Avanzi, N.; Ballinari, D.; Brasca, M.G.; Festuccia, C.; Fiorentini, F.; Locatelli, G.; Pastori, W.; Patton, V.; Roletto, F.; Colotta, F.; Galvani, A.; Isacchi, A.; Moll, J.; Pesenti, E.; Mercurio, C.; Ciomei, M. Dual targeting of CDK and tropomyosin receptor kinase families by the oral inhibitor PHA-848125, an agent with broad-spectrum antitumor efficacy. Mol. Cancer Ther., 2010, 9(8), 2243-2254.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0190] [PMID: 20682657]
[33]
Adnane, L.; Trail, P.A.; Taylor, I.; Wilhelm, S.M. Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol., 2006, 407, 597-612.
[http://dx.doi.org/10.1016/S0076-6879(05)07047-3] [PMID: 16757355]
[34]
Keating, G.M.; Santoro, A. Sorafenib. Drugs, 2009, 69(2), 223-240.
[http://dx.doi.org/10.2165/00003495-200969020-00006] [PMID: 19228077]
[35]
Zhu, A.X.; Duda, D.G.; Sahani, D.V.; Jain, R.K. Development of sunitinib in hepatocellular carcinoma: Rationale, early clinical experience, and correlative studies. Cancer J., 2009, 15(4), 263-268.
[http://dx.doi.org/10.1097/PPO.0b013e3181af5e35] [PMID: 19672141]
[36]
Liu, T.; Liu, R.; Zhang, S.; Guo, K.; Zhang, Q.; Li, W.; Liu, Y. Sorafenib induced alteration of protein glycosylation in hepatocellular carcinoma cells. Oncol. Lett., 2017, 14(1), 517-524.
[http://dx.doi.org/10.3892/ol.2017.6177] [PMID: 28693200]
[37]
Zhai, B.; Sun, X.Y. Mechanisms of resistance to sorafenib and the corresponding strategies in hepatocellular carcinoma. World J. Hepatol., 2013, 5(7), 345-352.
[http://dx.doi.org/10.4254/wjh.v5.i7.345] [PMID: 23898367]
[38]
Cheng, A.L.; Kang, Y.K.; Lin, D.Y.; Park, J.W.; Kudo, M.; Qin, S.; Chung, H.C.; Song, X.; Xu, J.; Poggi, G.; Omata, M.; Pitman, L.S.; Lanzalone, S.; Yang, L.; Lechuga, M.J.; Raymond, E. Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial. J. Clin. Oncol., 2013, 31(32), 4067-4075.
[http://dx.doi.org/10.1200/JCO.2012.45.8372] [PMID: 24081937]
[39]
Bruix, J.; Tak, W.Y.; Gasbarrini, A.; Santoro, A.; Colombo, M.; Lim, H.Y.; Mazzaferro, V.; Wiest, R.; Reig, M.; Wagner, A.; Bolondi, L. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase II safety study. Eur. J. Cancer, 2013, 49(16), 3412-3419.
[http://dx.doi.org/10.1016/j.ejca.2013.05.028] [PMID: 23809766]
[40]
Tai, W.T.; Chu, P.Y.; Shiau, C.W.; Chen, Y.L.; Li, Y.S.; Hung, M.H.; Chen, L.J.; Chen, P.L.; Su, J.C.; Lin, P.Y.; Yu, H.C.; Chen, K.F. STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma. Clin. Cancer Res., 2014, 20(22), 5768-5776.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0725] [PMID: 25248379]
[41]
Bruix, J.; Qin, S.; Merle, P.; Granito, A.; Huang, Y.H.; Bodoky, G.; Pracht, M.; Yokosuka, O.; Rosmorduc, O.; Breder, V.; Gerolami, R.; Masi, G.; Ross, P.J.; Song, T.; Bronowicki, J.P.; Ollivier-Hourmand, I.; Kudo, M.; Cheng, A.L.; Llovet, J.M.; Finn, R.S.; LeBerre, M.A.; Baumhauer, A.; Meinhardt, G.; Han, G. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2017, 389(10064), 56-66.
[http://dx.doi.org/10.1016/S0140-6736(16)32453-9] [PMID: 27932229]
[42]
Kudo, M. Immune checkpoint blockade in hepatocellular carcinoma: 2017 update. Liver Cancer, 2017, 6(1), 1-12.
[http://dx.doi.org/10.1159/000449342] [PMID: 27995082]
[43]
El-Khoueiry, A.B.; Sangro, B.; Yau, T.; Crocenzi, T.S.; Kudo, M.; Hsu, C.; Kim, T.Y.; Choo, S.P.; Trojan, J.; Welling, T.H., III; Meyer, T.; Kang, Y.K.; Yeo, W.; Chopra, A.; Anderson, J.; dela Cruz, C.; Lang, L.; Neely, J.; Tang, H.; Dastani, H.B.; Melero, I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet, 2017, 389(10088), 2492-2502.
[http://dx.doi.org/10.1016/S0140-6736(17)31046-2] [PMID: 28434648]
[44]
Yamamoto, Y.; Matsui, J.; Matsushima, T.; Obaishi, H.; Miyazaki, K.; Nakamura, K.; Tohyama, O.; Semba, T.; Yamaguchi, A.; Hoshi, S.; Mimura, F.; Haneda, T.; Fukuda, Y.; Kamata, J.; Takahashi, K.; Matsukura, M.; Wakabayashi, T.; Asada, M.; Nomoto, K.; Watanabe, T.; Dezso, Z.; Yoshimatsu, K.; Funahashi, Y.; Tsuruoka, A. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc. Cell, 2014, 6(1), 18.
[http://dx.doi.org/10.1186/2045-824X-6-18] [PMID: 25197551]
[45]
Ikeda, K.; Kudo, M.; Kawazoe, S.; Osaki, Y.; Ikeda, M.; Okusaka, T.; Tamai, T.; Suzuki, T.; Hisai, T.; Hayato, S.; Okita, K.; Kumada, H. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J. Gastroenterol., 2017, 52(4), 512-519.
[http://dx.doi.org/10.1007/s00535-016-1263-4] [PMID: 27704266]
[46]
Nakazawa, Y.; Kawano, S.; Matsui, J.; Funahashi, Y.; Tohyama, O.; Muto, H.; Nakagawa, T.; Matsushima, T. Multitargeting strategy using lenvatinib and golvatinib: Maximizing anti‐angiogenesis activity in a preclinical cancer model. Cancer Sci., 2015, 106(2), 201-207.
[http://dx.doi.org/10.1111/cas.12581] [PMID: 25458359]
[47]
Cochin, V.; Gross-Goupil, M.; Ravaud, A.; Godbert, Y.; Le Moulec, S. Cabozantinib: Modalités d’action, efficacité et indications. Bull. Cancer, 2017, 104(5), 393-401.
[http://dx.doi.org/10.1016/j.bulcan.2017.03.013] [PMID: 28477875]
[48]
Schöffski, P.; Gordon, M.; Smith, D.C.; Kurzrock, R.; Daud, A.; Vogelzang, N.J.; Lee, Y.; Scheffold, C.; Shapiro, G.I. Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Eur. J. Cancer, 2017, 86, 296-304.
[http://dx.doi.org/10.1016/j.ejca.2017.09.011] [PMID: 29059635]
[49]
Zhu, A.X.; Finn, R.S.; Edeline, J.; Cattan, S.; Ogasawara, S.; Palmer, D.; Verslype, C.; Zagonel, V.; Fartoux, L.; Vogel, A.; Sarker, D.; Verset, G.; Chan, S.L.; Knox, J.; Daniele, B.; Webber, A.L.; Ebbinghaus, S.W.; Ma, J.; Siegel, A.B.; Cheng, A.L.; Kudo, M.; Alistar, A.; Asselah, J.; Blanc, J-F.; Borbath, I.; Cannon, T.; Chung, K.; Cohn, A.; Cosgrove, D.P.; Damjanov, N.; Gupta, M.; Karino, Y.; Karwal, M.; Kaubisch, A.; Kelley, R.; Van Laethem, J-L.; Larson, T.; Lee, J.; Li, D.; Manhas, A.; Manji, G.A.; Numata, K.; Parsons, B.; Paulson, A.S.; Pinto, C.; Ramirez, R.; Ratnam, S.; Rizell, M.; Rosmorduc, O.; Sada, Y.; Sasaki, Y.; Stal, P.I.; Strasser, S.; Trojan, J.; Vaccaro, G.; Van, V.H.; Weiss, A.; Weiss, K-H.; Yamashita, T. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol., 2018, 19(7), 940-952.
[http://dx.doi.org/10.1016/S1470-2045(18)30351-6] [PMID: 29875066]
[50]
Kudo, M.; Hatano, E.; Ohkawa, S.; Fujii, H.; Masumoto, A.; Furuse, J.; Wada, Y.; Ishii, H.; Obi, S.; Kaneko, S.; Kawazoe, S.; Yokosuka, O.; Ikeda, M.; Ukai, K.; Morita, S.; Tsuji, A.; Kudo, T.; Shimada, M.; Osaki, Y.; Tateishi, R.; Sugiyama, G.; Abada, P.B.; Yang, L.; Okusaka, T.; Zhu, A.X. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial. J. Gastroenterol., 2017, 52(4), 494-503.
[http://dx.doi.org/10.1007/s00535-016-1247-4] [PMID: 27549242]
[51]
Zhu, A.X.; Finn, R.S.; Mulcahy, M.; Gurtler, J.; Sun, W.; Schwartz, J.D.; Dalal, R.P.; Joshi, A.; Hozak, R.R.; Xu, Y.; Ancukiewicz, M.; Jain, R.K.; Nugent, F.W.; Duda, D.G.; Stuart, K. A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer. Clin. Cancer Res., 2013, 19(23), 6614-6623.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1442] [PMID: 24088738]
[52]
Herbst, R.S.; Soria, J.C.; Kowanetz, M.; Fine, G.D.; Hamid, O.; Gordon, M.S.; Sosman, J.A.; McDermott, D.F.; Powderly, J.D.; Gettinger, S.N.; Kohrt, H.E.K.; Horn, L.; Lawrence, D.P.; Rost, S.; Leabman, M.; Xiao, Y.; Mokatrin, A.; Koeppen, H.; Hegde, P.S.; Mellman, I.; Chen, D.S.; Hodi, F.S. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528), 563-567.
[http://dx.doi.org/10.1038/nature14011] [PMID: 25428504]
[53]
Chen, D.S.; Irving, B.A.; Hodi, F.S. Molecular pathways: Next-generation immunotherapy inhibiting programmed death-ligand 1 and programmed death-1. Clin. Cancer Res., 2012, 18(24), 6580-6587.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1362] [PMID: 23087408]
[54]
Egen, J.G.; Kuhns, M.S.; Allison, J.P. CTLA-4: New insights into its biological function and use in tumor immunotherapy. Nat. Immunol., 2002, 3(7), 611-618.
[http://dx.doi.org/10.1038/ni0702-611] [PMID: 12087419]
[55]
Aspeslagh, S.; Shailubhai, K.; Bahleda, R.; Gazzah, A.; Varga, A.; Hollebecque, A.; Massard, C.; Spreafico, A.; Reni, M.; Soria, J.C. Phase I dose-escalation study of milciclib in combination with gemcitabine in patients with refractory solid tumors. Cancer Chemother. Pharmacol., 2017, 79(6), 1257-1265.
[http://dx.doi.org/10.1007/s00280-017-3303-z] [PMID: 28424962]
[56]
Hsieh, F.S.; Chen, Y.L.; Hung, M.H.; Chu, P.Y.; Tsai, M.H.; Chen, L.J.; Hsiao, Y.J.; Shih, C.T.; Chang, M.J.; Chao, T.I.; Shiau, C.W.; Chen, K.F. Palbociclib induces activation of AMPK and inhibits hepatocellular carcinoma in a CDK4/6-independent manner. Mol. Oncol., 2017, 11(8), 1035-1049.
[http://dx.doi.org/10.1002/1878-0261.12072] [PMID: 28453226]
[57]
Bollard, J.; Miguela, V.; Ruiz de Galarreta, M.; Venkatesh, A.; Bian, C.B.; Roberto, M.P.; Tovar, V.; Sia, D.; Molina-Sánchez, P.; Nguyen, C.B.; Nakagawa, S.; Llovet, J.M.; Hoshida, Y.; Lujambio, A. Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma. Gut, 2017, 66(7), 1286-1296.
[http://dx.doi.org/10.1136/gutjnl-2016-312268] [PMID: 27849562]
[58]
Herbertz, S.; Sawyer, J.S.; Stauber, A.J.; Gueorguieva, I.; Driscoll, K.E.; Estrem, S.T.; Cleverly, A.L.; Desaiah, D.; Guba, S.C.; Benhadji, K.A.; Slapak, C.A.; Lahn, M.M. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway. Drug Des. Devel. Ther., 2015, 9, 4479-4499.
[PMID: 26309397]
[59]
Anido, J.; Sáez-Borderías, A.; Gonzàlez-Juncà, A.; Rodón, L.; Folch, G.; Carmona, M.A.; Prieto-Sánchez, R.M.; Barba, I.; Martínez-Sáez, E.; Prudkin, L.; Cuartas, I.; Raventós, C.; Martínez-Ricarte, F.; Poca, M.A.; García-Dorado, D.; Lahn, M.M.; Yingling, J.M.; Rodón, J.; Sahuquillo, J.; Baselga, J.; Seoane, J. TGF-beta receptor inhibitors target the CD44(high)/Id1(high) glioma-initiating cell population in human glioblastoma. Cancer Cell, 2010, 18(6), 655-668.
[http://dx.doi.org/10.1016/j.ccr.2010.10.023] [PMID: 21156287]
[60]
Peñuelas, S.; Anido, J.; Prieto-Sánchez, R.M.; Folch, G.; Barba, I.; Cuartas, I.; García-Dorado, D.; Poca, M.A.; Sahuquillo, J.; Baselga, J.; Seoane, J. TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell, 2009, 15(4), 315-327.
[http://dx.doi.org/10.1016/j.ccr.2009.02.011] [PMID: 19345330]
[61]
Hardee, M.E.; Marciscano, A.E.; Medina-Ramirez, C.M.; Zagzag, D.; Narayana, A.; Lonning, S.M.; Barcellos-Hoff, M.H. Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-β. Cancer Res., 2012, 72(16), 4119-4129.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-0546] [PMID: 22693253]
[62]
Le, P.N.; McDermott, J.D.; Jimeno, A. Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28. Pharmacol. Ther., 2015, 146, 1-11.
[http://dx.doi.org/10.1016/j.pharmthera.2014.08.005] [PMID: 25172549]
[63]
Jimeno, A.; Gordon, M.; Chugh, R.; Messersmith, W.; Mendelson, D.; Dupont, J.; Stagg, R.; Kapoun, A.M.; Xu, L.; Uttamsingh, S.; Brachmann, R.K.; Smith, D.C. A first-in-human Phase 1 study of the anti-cancer stem cell agent ipafricept (OMP-54F28), a decoy receptor for Wnt ligands, in patients with advanced solid tumors. Clin. Cancer Res., 2017, 23(24), 7490-7497.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2157] [PMID: 28954784]
[64]
Johnson, P.J.; Qin, S.; Park, J.W.; Poon, R.T.P.; Raoul, J.L.; Philip, P.A.; Hsu, C.H.; Hu, T.H.; Heo, J.; Xu, J.; Lu, L.; Chao, Y.; Boucher, E.; Han, K.H.; Paik, S.W.; Robles-Aviña, J.; Kudo, M.; Yan, L.; Sobhonslidsuk, A.; Komov, D.; Decaens, T.; Tak, W.Y.; Jeng, L.B.; Liu, D.; Ezzeddine, R.; Walters, I.; Cheng, A.L. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study. J. Clin. Oncol., 2013, 31(28), 3517-3524.
[http://dx.doi.org/10.1200/JCO.2012.48.4410] [PMID: 23980084]
[65]
Llovet, J.M.; Decaens, T.; Raoul, J.L.; Boucher, E.; Kudo, M.; Chang, C.; Kang, Y.K.; Assenat, E.; Lim, H.Y.; Boige, V.; Mathurin, P.; Fartoux, L.; Lin, D.Y.; Bruix, J.; Poon, R.T.; Sherman, M.; Blanc, J.F.; Finn, R.S.; Tak, W.Y.; Chao, Y.; Ezzeddine, R.; Liu, D.; Walters, I.; Park, J.W. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: Results from the randomized phase III BRISK-PS study. J. Clin. Oncol., 2013, 31(28), 3509-3516.
[http://dx.doi.org/10.1200/JCO.2012.47.3009] [PMID: 23980090]
[66]
Kudo, M.; Han, G.; Finn, R.S.; Poon, R.T.P.; Blanc, J.F.; Yan, L.; Yang, J.; Lu, L.; Tak, W.Y.; Yu, X.; Lee, J.H.; Lin, S.M.; Wu, C.; Tanwandee, T.; Shao, G.; Walters, I.B.; Dela Cruz, C.; Poulart, V.; Wang, J.H. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial. Hepatology, 2014, 60(5), 1697-1707.
[http://dx.doi.org/10.1002/hep.27290] [PMID: 24996197]
[67]
Cainap, C.; Qin, S.; Huang, W.T.; Chung, I.J.; Pan, H.; Cheng, Y.; Kudo, M.; Kang, Y.K.; Chen, P.J.; Toh, H.C.; Gorbunova, V.; Eskens, F.A.L.M.; Qian, J.; McKee, M.D.; Ricker, J.L.; Carlson, D.M.; El-Nowiem, S. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial. J. Clin. Oncol., 2015, 33(2), 172-179.
[http://dx.doi.org/10.1200/JCO.2013.54.3298] [PMID: 25488963]
[68]
Yoon, Y.K.; Ali, M.A.; Wei, A.C.; Shirazi, A.N.; Parang, K.; Choon, T.S. Benzimidazoles as new scaffold of sirtuin inhibitors: Green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. Eur. J. Med. Chem., 2014, 83, 448-454.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.060] [PMID: 24992072]
[69]
Rawat, S.; Ghate, M. Potential anticancer agents from benzimidazole derivatives. Nat. Volatiles Essent. Oils, 2021, 8(6), 4109-4120.
[70]
Gao, C.; Li, B.; Zhang, B.; Sun, Q.; Li, L.; Li, X.; Chen, C.; Tan, C.; Liu, H.; Jiang, Y. Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents. Bioorg. Med. Chem., 2015, 23(8), 1800-1807.
[http://dx.doi.org/10.1016/j.bmc.2015.02.036] [PMID: 25778766]
[71]
Shao, K.P.; Zhang, X.Y.; Chen, P.J.; Xue, D.Q.; He, P.; Ma, L.Y.; Zheng, J.X.; Zhang, Q.R.; Liu, H.M. Synthesis and biological evaluation of novel pyrimidine–benzimidazol hybrids as potential anticancer agents. Bioorg. Med. Chem. Lett., 2014, 24(16), 3877-3881.
[http://dx.doi.org/10.1016/j.bmcl.2014.06.050] [PMID: 25001482]
[72]
Luo, Y.; Xiao, F.; Qian, S.; Lu, W.; Yang, B. Synthesis and in vitro cytotoxic evaluation of some thiazolylbenzimidazole derivatives. Eur. J. Med. Chem., 2011, 46(1), 417-422.
[http://dx.doi.org/10.1016/j.ejmech.2010.11.014] [PMID: 21115212]
[73]
Yuan, X.; Yang, Q.; Liu, T.; Li, K.; Liu, Y.; Zhu, C.; Zhang, Z.; Li, L.; Zhang, C.; Xie, M.; Lin, J.; Zhang, J.; Jin, Y. Design, synthesis and in vitro evaluation of 6-amide-2-aryl benzoxazole/benzimidazole derivatives against tumor cells by inhibiting VEGFR-2 kinase. Eur. J. Med. Chem., 2019, 179, 147-165.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.054] [PMID: 31252306]
[74]
Kumar, D.; Kumar, N.M.; Sundaree, S.; Johnson, E.O.; Shah, K. An expeditious synthesis and anticancer activity of novel 4-(3′-indolyl)oxazoles. Eur. J. Med. Chem., 2010, 45(3), 1244-1249.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.024] [PMID: 20047778]
[75]
Ke, S.; Yang, Z.; Zhang, Z.; Liang, Y.; Wang, K.; Liu, M.; Shi, L. Multisubstituted indole–acrylonitrile hybrids as potential cytotoxic agents. Bioorg. Med. Chem. Lett., 2014, 24(8), 1907-1911.
[http://dx.doi.org/10.1016/j.bmcl.2014.03.011] [PMID: 24684840]
[76]
Mphahlele, M.J.; Mmakwena, M.M.; Abimbola, A. Synthesis, biological evaluation and molecular docking of novel indole-aminoquinazoline hybrids for anticancer properties. Int. J. Mol. Sci., 2018, 19(8), 2232.
[http://dx.doi.org/10.3390/ijms19082232] [PMID: 30065164]
[77]
Hawash, M.; Kahraman, D.C.; Ergun, S.G.; Atalay, R.C. Synthesis of novel indole - isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines. BMC Chem., 2021, 15(1), 66.
[http://dx.doi.org/10.1186/s13065-021-00793-8] [PMID: 34930409]
[78]
Hu, F.; Szostak, M. Recent developments in the synthesis and reactivity of isoxazoles: Metal catalysis and beyond. Adv. Synth. Catal., 2015, 357(12), 2583-2614.
[http://dx.doi.org/10.1002/adsc.201500319]
[79]
İbiş, K.; Nalbat, E.; Çalışkan, B.; Kahraman, D.C.; Cetin-Atalay, R.; Banoglu, E. Synthesis and biological evaluation of novel isoxazole-piperazine hybrids as potential anti-cancer agents with inhibitory effect on liver cancer stem cells. Eur. J. Med. Chem., 2021, 221, 113489.
[http://dx.doi.org/10.1016/j.ejmech.2021.113489] [PMID: 33951549]
[80]
Shi, L.; Hu, R.; Wei, Y.; Liang, Y.; Yang, Z.; Ke, S. Anthranilic acid-based diamides derivatives incorporating aryl-isoxazoline pharmacophore as potential anticancer agents: Design, synthesis and biological evaluation. Eur. J. Med. Chem., 2012, 54, 549-556.
[http://dx.doi.org/10.1016/j.ejmech.2012.06.001] [PMID: 22727445]
[81]
Ghanaat, J.; Khalilzadeh, M.A.; Zareyee, D. Molecular docking studies, biological evaluation and synthesis of novel 3-mercapto-1,2,4-triazole derivatives. Mol. Divers., 2021, 25(1), 223-232.
[http://dx.doi.org/10.1007/s11030-020-10050-0] [PMID: 32067134]
[82]
Du, Q.R.; Li, D.D.; Pi, Y.Z.; Li, J.R.; Sun, J.; Fang, F.; Zhong, W.Q.; Gong, H.B.; Zhu, H.L. Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents. Bioorg. Med. Chem., 2013, 21(8), 2286-2297.
[http://dx.doi.org/10.1016/j.bmc.2013.02.008] [PMID: 23490159]
[83]
Madhavilatha, B.; Bhattacharjee, D.; Sabitha, G.; Reddy, B.V.S.; Yadav, J.S.; Jain, N.; Reddy, B.J.M. Synthesis and in vitro anticancer activity of novel 1,3,4-oxadiazole-linked 1,2,3-Triazole/Isoxazole hybrids. J. Heterocycl. Chem., 2018, 55(4), 863-870.
[http://dx.doi.org/10.1002/jhet.3110]
[84]
Arafa, R.K.; Hegazy, G.H.; Piazza, G.A.; Abadi, A.H. Synthesis and in vitro antiproliferative effect of novel quinoline-based potential anticancer agents. Eur. J. Med. Chem., 2013, 63, 826-832.
[http://dx.doi.org/10.1016/j.ejmech.2013.03.008] [PMID: 23584545]
[85]
Li, S.; Huang, Q.; Liu, Y.; Zhang, X.; Liu, S.; He, C.; Gong, P. Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety. Eur. J. Med. Chem., 2013, 64, 62-73.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.001] [PMID: 23644189]
[86]
Helal, M.H.; El-Awdan, S.A.; Salem, M.A.; Abd-elaziz, T.A.; Moahamed, Y.A.; El-Sherif, A.A.; Mohamed, G.A.M. Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2015, 135, 764-773.
[http://dx.doi.org/10.1016/j.saa.2014.06.145] [PMID: 25150427]
[87]
Chen, T.; Luo, Y.; Hu, Y.; Yang, B.; Lu, W. Synthesis and biological evaluation of novel 1,6-diaryl pyridin-2(1H)-one analogs. Eur. J. Med. Chem., 2013, 64, 613-620.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.008] [PMID: 23708235]
[88]
Ahmed, N.M.; Youns, M.; Soltan, M.K.; Said, A.M. Design, synthesis, molecular modelling, and biological evaluation of novel substituted pyrimidine derivatives as potential anticancer agents for hepatocellular carcinoma. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1110-1120.
[http://dx.doi.org/10.1080/14756366.2019.1612889] [PMID: 31117890]
[89]
Sondhi, S.M.; Singh, J.; Rani, R.; Gupta, P.P.; Agrawal, S.K.; Saxena, A.K. Synthesis, anti-inflammatory and anticancer activity evaluation of some novel acridine derivatives. Eur. J. Med. Chem., 2010, 45(2), 555-563.
[http://dx.doi.org/10.1016/j.ejmech.2009.10.042] [PMID: 19926172]
[90]
Lang, X.; Li, L.; Chen, Y.; Sun, Q.; Wu, Q.; Liu, F.; Tan, C.; Liu, H.; Gao, C.; Jiang, Y. Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents. Bioorg. Med. Chem., 2013, 21(14), 4170-4177.
[http://dx.doi.org/10.1016/j.bmc.2013.05.008] [PMID: 23735826]

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