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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Review Article

Benzimidazole: A Multifacted Nucelus for Anticancer Agents

Author(s): Yogita Bansal*, Richa Minhas, Ankit Singhal, Radhey Krishan Arora and Gulshan Bansal

Volume 25, Issue 6, 2021

Published on: 08 February, 2021

Page: [669 - 694] Pages: 26

DOI: 10.2174/1385272825666210208141107

Price: $65

Abstract

Cancer is characterized by an uncontrolled proliferation of cells, dedifferentiation, invasiveness and metastasis. Endothelial growth factor (eGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF), checkpoint kinase 1 & 2 ( Chk1 & Chk2), aurora kinases, topoisomerases, histone deacetylators (HDAC), poly(ADP-Ribose)polymerase (PARP), farnesyl transferases, RAS-MAPK pathway and PI3K-Akt-mTOR pathway, are some of the prominent mediators implicated in the proliferation of tumor cells. Huge artillery of natural and synthetic compounds as anticancer, which act by inhibiting one or more of the enzymes and/or pathways responsible for the progression of tumor cells, is reported in the literature. The major limitations of anticancer agents used in clinics as well as of those under development in literature are normal cell toxicity and other side effects due to lack of specificity. Hence, medicinal chemists across the globe have been working for decades to develop potent and safe anticancer agents from natural sources as well as from different classes of heterocycles. Benzimidazole is one of the most important and explored heteronucelus because of their versatility in biological actions as well as synthetic applications in medicinal chemistry. The structural similarity of amino derivatives of benzimidazole with purines makes it a fascinating nucleus for the development of anticancer, antimicrobial and anti-HIV agents. This review article is an attempt to critically analyze various reports on benzimidazole derivatives acting on different targets to act as anticancer so as to understand the structural requirements around benzimidazole nucleus for each target and enable medicinal chemists to promote rational development of antitumor agents.

Keywords: Uncontrolled proliferation, checkpoint kinase, aurora kinases, topoisomerases, MAPK pathway, benzimidazoles.

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[1]
Goud, N.S.; Kumar, P.; Bharath, R.D. Recent developments of target-based benzimidazole derivatives as potential anticancer agents.Heterocycles-Synthesis and Biological Activities; IntechOpen, 2020.
[http://dx.doi.org/10.5772/intechopen.90758]
[2]
Yu, B.; Yu, D.Q.; Liu, H.M. Spirooxindoles: promising scaffolds for anticancer agents. Eur. J. Med. Chem., 2015, 97, 673-698.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.056] [PMID: 24994707]
[3]
Nepali, K.; Sharma, S.; Sharma, M.; Bedi, P.M.S.; Dhar, K.L. references Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur. J. Med. Chem., 2014, 77, 422-487.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.018] [PMID: 24685980]
[4]
Zhang, Q.; Zhu, B.; Li, Y. Resolution of cancer-promoting inflammation: a new approach for anticancer therapy. Front. Immunol., 2017, 8, 71.
[http://dx.doi.org/10.3389/fimmu.2017.00071] [PMID: 28210259]
[5]
Aziz, M.A.; Serya, R.A.; Lasheen, D.S.; Abouzid, K.A. Furo[2,3-d]pyrimidine based derivatives as kinase inhibitors and anticancer agents. Future J. Pharm. Sci., 2016, 2, 1-8.
[http://dx.doi.org/10.1016/j.fjps.2015.12.001]
[6]
Ismail, N.S.; Ali, E.M.; Ibrahim, D.A.; Serya, R.A.; Abou El Ella, D.A. Pyrazolo[3,4-d]pyrimidine based scaffold derivatives targeting kinases as anticancer agents. Future J. Pharm. Sci., 2016, 2, 20-30.
[http://dx.doi.org/10.1016/j.fjps.2016.02.002]
[7]
Ismail, N.S.; Ali, G.M.; Ibrahim, D.A.; Elmetwali, A.M. Medicinal attributes of pyrazolo[1, 5-a]pyrimidine based scaffold derivatives targeting kinases as anticancer agents. Future J. Pharm. Sci., 2016, 2, 60-70.
[http://dx.doi.org/10.1016/j.fjps.2016.08.004]
[8]
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, 4920-4946.
[http://dx.doi.org/10.1016/j.arabjc.2016.10.009]
[9]
Cherukupalli, S.; Karpoormath, R.; Chandrasekaran, B.; Hampannavar, G.A.; Thapliyal, N.; Palakollu, V.N. An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine scaffold. Eur. J. Med. Chem., 2017, 126, 298-352.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.019] [PMID: 27894044]
[10]
Belal, A. El-Gendy, Bel-D. Pyrrolizines: promising scaffolds for anticancer drugs. Bioorg. Med. Chem., 2014, 22(1), 46-53.
[http://dx.doi.org/10.1016/j.bmc.2013.11.040] [PMID: 24331756]
[11]
Ismail, R.S.; Ismail, N.S.; Abuserii, S.; Abou El Ella, D.A. Recent advances in 4-aminoquinazoline based scaffold derivatives targeting EGFR kinases as anticancer agents. Future J. Pharm. Sci., 2016, 2, 9-19.
[http://dx.doi.org/10.1016/j.fjps.2016.02.001]
[12]
El Rashedy, A.A.; Aboul-Enein, H.Y. Benzimidazole derivatives as potential anticancer agents. Mini Rev. Med. Chem., 2013, 13(3), 399-407.
[PMID: 23190032]
[13]
Chu, B.; Liu, F.; Li, L.; Ding, C.; Chen, K.; Sun, Q.; Shen, Z.; Tan, Y.; Tan, C.; Jiang, Y. A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2 activity and upregulates DR5 in breast cancer cells. Cell Death Dis., 2015, 6(3)e1686
[http://dx.doi.org/10.1038/cddis.2015.25] [PMID: 25766325]
[14]
Son, D.S.; Lee, E.S.; Adunyah, S.E. The antitumor potentials of benzimidazole anthelmintics as repurposing drugs. Immune Netw., 2020, 20(4)e29
[http://dx.doi.org/10.4110/in.2020.20.e29] [PMID: 32895616]
[15]
Yadav, S.; Narasimhan, B. 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 ]
[16]
Kanwal, A.; Saddique, F.A.; Aslam, S.; Ahmad, M.; Zahoor, A.F. Benzimidazole ring system as a privileged template for anticancer agents. Pharm. Chem. J., 2018, 51(12), 1068-1077.
[http://dx.doi.org/10.1007/s11094-018-1742-4]
[17]
Tahlan, S.; Kumar, S.; Kakkar, S.; Narasimhan, B. Benzimidazole scaffolds as promising antiproliferative agents: a review. BMC Chem., 2019, 13(1), 66.
[http://dx.doi.org/10.1186/s13065-019-0579-6] [PMID: 31384813]
[18]
Ali, E.M.H.; Abdel-Maksoud, M.S.; Oh, C.H. Thieno[2,3-d]pyrimidine as a promising scaffold in medicinal chemistry: recent advances. Bioorg. Med. Chem., 2019, 27(7), 1159-1194.
[http://dx.doi.org/10.1016/j.bmc.2019.02.044] [PMID: 30826188]
[19]
Arshad, F.; Khan, M.F.; Akhtar, W.; Alam, M.M.; Nainwal, L.M.; Kaushik, S.K.; Akhter, M.; Parvez, S.; Hasan, S.M.; Shaquiquzzaman, M. Revealing quinquennial anticancer journey of morpholine: a SAR based review. Eur. J. Med. Chem., 2019, 167, 324-356.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.015] [PMID: 30776694]
[20]
Bennani, F.E.; Doudach, L.; Cherrah, Y.; Ramli, Y.; Karrouchi, K.; Ansar, M.; Faouzi, M.E.A. Overview of recent developments of pyrazole derivatives as an anticancer agent in different cell line. Bioorg. Chem., 2020, 97103470
[http://dx.doi.org/10.1016/j.bioorg.2019.103470] [PMID: 32120072]
[21]
Cao, H.; Li, L.; Yang, D.; Zeng, L.; Yewei, X.; Yu, B.; Liao, G.; Chen, J. Recent progress in histone methyltransferase (G9a) inhibitors as anticancer agents. Eur. J. Med. Chem., 2019, 179, 537-546.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.072] [PMID: 31276898]
[22]
Das, D.; Hong, J. Recent advancements of 4-aminoquinazoline derivatives as kinase inhibitors and their applications in medicinal chemistry. Eur. J. Med. Chem., 2019, 170, 55-72.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.004] [PMID: 30878832]
[23]
Golonko, A.; Lewandowska, H.; Świsłocka, R.; Jasińska, U.T.; Priebe, W.; Lewandowski, W. Curcumin as tyrosine kinase inhibitor in cancer treatment. Eur. J. Med. Chem., 2019, 181111512
[http://dx.doi.org/10.1016/j.ejmech.2019.07.015] [PMID: 31404861]
[24]
Liang, X.; Wu, Q.; Luan, S.; Yin, Z.; He, C.; Yin, L.; Zou, Y.; Yuan, Z.; Li, L.; Song, X.; He, M.; Lv, C.; Zhang, W. A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. Eur. J. Med. Chem., 2019, 171, 129-168.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.034] [PMID: 30917303]
[25]
Qiao, Y.; Chen, T.; Yang, H.; Chen, Y.; Lin, H.; Qu, W.; Feng, F.; Liu, W.; Guo, Q.; Liu, Z.; Sun, H. Small molecule modulators targeting protein kinase CK1 and CK2. Eur. J. Med. Chem., 2019, 181111581
[http://dx.doi.org/10.1016/j.ejmech.2019.111581] [PMID: 31400711]
[26]
Roskoski, R. Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacol. Res., 2019, 139, 395-411.
[http://dx.doi.org/10.1016/j.phrs.2018.11.014] [PMID: 30500458]
[27]
Xu, Z.; Zhao, S.J.; Liu, Y. 1,2,3-Triazole-containing hybrids as potential anticancer agents: Current developments, action mechanisms and structure-activity relationships. Eur. J. Med. Chem., 2019, 183111700
[http://dx.doi.org/10.1016/j.ejmech.2019.111700] [PMID: 31546197]
[28]
Yin, B.; Fang, D.M.; Zhou, X.L.; Gao, F. Natural products as important tyrosine kinase inhibitors. Eur. J. Med. Chem., 2019, 182111664
[http://dx.doi.org/10.1016/j.ejmech.2019.111664] [PMID: 31494475]
[29]
Gao, F.; Sun, Z.; Kong, F.; Xiao, J. Artemisinin-derived hybrids and their anticancer activity. Eur. J. Med. Chem., 2020, 188112044
[http://dx.doi.org/10.1016/j.ejmech.2020.112044] [PMID: 31945642]
[30]
Wang, R.; Chen, H.; Yan, W.; Zheng, M.; Zhang, T.; Zhang, Y. Ferrocene-containing hybrids as potential anticancer agents: current developments, mechanisms of action and structure-activity relationships. Eur. J. Med. Chem., 2020, 190112109
[http://dx.doi.org/10.1016/j.ejmech.2020.112109] [PMID: 32032851]
[31]
Narasimhan, B.; Sharma, D.; Kumar, P. Benzimidazole: a medicinally important heterocyclic moiety. Med. Chem. Res., 2012, 21, 269-283.
[http://dx.doi.org/10.1007/s00044-010-9533-9]
[32]
Bansal, Y.; Silakari, O. The therapeutic journey of benzimidazoles: a review. Bioorg. Med. Chem., 2012, 20(21), 6208-6236.
[http://dx.doi.org/10.1016/j.bmc.2012.09.013] [PMID: 23031649]
[33]
Gaba, M.; Singh, S.; Mohan, C. Benzimidazole: an emerging scaffold for analgesic and anti-inflammatory agents. Eur. J. Med. Chem., 2014, 76, 494-505.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.030] [PMID: 24602792]
[34]
Kaur, G.; Kaur, M.; Silakari, O. Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted anti-inflammatory ligands. Mini Rev. Med. Chem., 2014, 14(9), 747-767.
[http://dx.doi.org/10.2174/1389557514666140820120518] [PMID: 25138088]
[35]
Keri, R.S.; Rajappa, C.K.; Patil, S.A.; Nagaraja, B.M. Benzimidazole-core as an antimycobacterial agent. Pharmacol. Rep., 2016, 68(6), 1254-1265.
[http://dx.doi.org/10.1016/j.pharep.2016.08.002] [PMID: 27686965]
[36]
Shaharyar, M.; Mazumder, A. Benzimidazoles: a biologically active compounds. Arab. J. Chem., 2017, 10, S157-S173.
[http://dx.doi.org/10.1016/j.arabjc.2012.07.017]
[37]
Singh, P.K.; Silakari, O. Benzimidazole: journey from single targeting to multitargeting molecule In: Key Heterocycle Cores for Designing Multitargeting Molecules; 1st ed., Elsevier; , 2018; pp. 31-52.
[38]
Purushottamachar, P.; Ramalingam, S.; Njar, V.C. Development of benzimidazole compounds for cancer therapy.Chemistry and Applications of Benzimidazole and Its Derivatives; IntechOpen, 2019.
[http://dx.doi.org/10.5772/intechopen.86691]
[39]
Haddad, J.J. The immunopharmacologic potential of Semaxanib and new generation directed therapeutic drugs: receptor tyrosine kinase regulation with anti-tumorigenensis/angiogenesis properties. Saudi Pharm. J., 2012, 20(2), 103-123.
[http://dx.doi.org/10.1016/j.jsps.2011.09.002] [PMID: 23960782]
[40]
National Cancer Institute. Understanding Cancer and Related Topics., Available from:http://www.cancer.gov/cancertopics/understandingcancer/angiogenesis
[41]
Cao, Y. Molecular mechanisms and therapeutic development of angiogenesis inhibitors. Adv. Cancer Res., 2008, 100, 113-131.
[http://dx.doi.org/10.1016/S0065-230X(08)00004-3] [PMID: 18620094]
[42]
Dhillon, A.S.; Hagan, S.; Rath, O.; Kolch, W. MAP kinase signalling pathways in cancer. Oncogene, 2007, 26(22), 3279-3290.
[http://dx.doi.org/10.1038/sj.onc.1210421] [PMID: 17496922]
[43]
Yap, T.A.; Garrett, M.D.; Walton, M.I.; Raynaud, F.; de Bono, J.S.; Workman, P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr. Opin. Pharmacol., 2008, 8(4), 393-412.
[http://dx.doi.org/10.1016/j.coph.2008.08.004] [PMID: 18721898]
[44]
Wilhelm, S.; Carter, C.; Lynch, M.; Lowinger, T.; Dumas, J.; Smith, R.A.; Schwartz, B.; Simantov, R.; Kelley, S. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat. Rev. Drug Discov., 2006, 5(10), 835-844.
[http://dx.doi.org/10.1038/nrd2130] [PMID: 17016424]
[45]
Maione, P.; Gridelli, C.; Troiani, T.; Ciardiello, F. Combining targeted therapies and drugs with multiple targets in the treatment of NSCLC. Oncologist, 2006, 11(3), 274-284.
[http://dx.doi.org/10.1634/theoncologist.11-3-274] [PMID: 16549812]
[46]
Ricci, M.S.; Zong, W-X. Chemotherapeutic approaches for targeting cell death pathways. Oncologist, 2006, 11(4), 342-357.
[http://dx.doi.org/10.1634/theoncologist.11-4-342] [PMID: 16614230]
[47]
Medscape, Multispeciality Available from: http://www.medscape.org/viewarticle/559830
[48]
Yu, H.; Rohan, T. Role of the insulin-like growth factor family in cancer development and progression. J. Natl. Cancer Inst., 2000, 92(18), 1472-1489.
[http://dx.doi.org/10.1093/jnci/92.18.1472] [PMID: 10995803]
[49]
Furgason, J.M.; Bahassi, M. Targeting DNA repair mechanisms in cancer. Pharmacol. Ther., 2013, 137(3), 298-308.
[http://dx.doi.org/10.1016/j.pharmthera.2012.10.009] [PMID: 23107892]
[50]
Branzei, D.; Foiani, M. Regulation of DNA repair throughout the cell cycle. Nat. Rev. Mol. Cell Biol., 2008, 9(4), 297-308.
[http://dx.doi.org/10.1038/nrm2351] [PMID: 18285803]
[51]
Khalil, H.S.; Tummala, H.; Chakarov, S.; Zhelev, N.; Lane, D.P. Targeting ATM pathway for therapeutic intervention in cancer. Biodiscovery, 2012, 1, 1-13.
[http://dx.doi.org/10.7750/BioDiscovery.2012.1.3]
[52]
Ashwell, S.; Zabludoff, S. DNA damage detection and repair pathways--recent advances with inhibitors of checkpoint kinases in cancer therapy. Clin. Cancer Res., 2008, 14(13), 4032-4037.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5138] [PMID: 18593978]
[53]
Singh, M.; Tandon, V. Synthesis and biological activity of novel inhibitors of topoisomerase I: 2-aryl-substituted 2-bis-1H-benzimidazoles. Eur. J. Med. Chem., 2011, 46(2), 659-669.
[http://dx.doi.org/10.1016/j.ejmech.2010.11.046] [PMID: 21186067]
[54]
Alper, S. TemizArpaci, Ö.; Şener Aki, E.; Yalçin, I. Some new bi-and ter-benzimidazole derivatives as topoisomerase I inhibitors. Rev. Bras. Farmacogn., 2003, 58, 497-507.
[PMID: 12818688]
[55]
Cepeda, V.; Fuertes, M.A.; Castilla, J.; Alonso, C.; Quevedo, C.; Soto, M.; Pérez, J.M. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors in cancer chemotherapy. Recent Pat. Anticancer Drug Discov., 2006, 1(1), 39-53.
[http://dx.doi.org/10.2174/157489206775246430] [PMID: 18221025]
[56]
Penning, T.D.; Zhu, G-D.; Gandhi, V.B.; Gong, J.; Thomas, S.; Lubisch, W.; Grandel, R.; Wernet, W.; Park, C.H.; Fry, E.H.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E.F.; Donawho, C.K.; Frost, D.J.; Bontcheva-Diaz, V.; Bouska, J.J.; Olson, A.M.; Marsh, K.C.; Luo, Y.; Rosenberg, S.H.; Giranda, V.L. Discovery and SAR of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide: a potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer. Bioorg. Med. Chem., 2008, 16(14), 6965-6975.
[http://dx.doi.org/10.1016/j.bmc.2008.05.044] [PMID: 18541433]
[57]
Gautschi, O.; Heighway, J.; Mack, P.C.; Purnell, P.R.; Lara, P.N.; Gandara, D.R. Aurora kinases as anticancer drug targets. Clin. Cancer Res., 2008, 14(6), 1639-1648.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-2179] [PMID: 18347165]
[58]
Zheng, Y.; Zheng, M.; Ling, X.; Liu, Y.; Xue, Y.; An, L.; Gu, N.; Ji, M. Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole-benzimidazole derivatives as potent Aurora A/B kinase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(12), 3523-3530.
[http://dx.doi.org/10.1016/j.bmcl.2013.04.039] [PMID: 23664099]
[59]
Rewcastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Kendall, J.D.; Denny, W.A.; Baguley, B.C.; Buchanan, C.M.; Chao, M.; Kestell, P.; Kolekar, S.; Lee, W.J.; Lill, C.L.; Malik, A.; Singh, R.; Jamieson, S.M.; Shepherd, P.R. Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474). Eur. J. Med. Chem., 2013, 64, 137-147.
[http://dx.doi.org/10.1016/j.ejmech.2013.03.038] [PMID: 23644197]
[60]
Carvajal, R.D.; Tse, A.; Schwartz, G.K. Aurora kinases: new targets for cancer therapy. Clin. Cancer Res., 2006, 12(23), 6869-6875.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1405] [PMID: 17145803]
[61]
Katayama, H.; Brinkley, W.R.; Sen, S. The Aurora kinases: role in cell transformation and tumorigenesis. Cancer Metastasis Rev., 2003, 22(4), 451-464.
[http://dx.doi.org/10.1023/A:1023789416385] [PMID: 12884918]
[62]
Wang, H.; Yu, N.; Song, H.; Chen, D.; Zou, Y.; Deng, W.; Lye, P.L.; Chang, J.; Ng, M.; Sun, E.T.; Sangthongpitag, K.; Wang, X.; Wu, X.; Khng, H.H.; Fang, L.; Goh, S.K.; Ong, W.C.; Bonday, Z.; Stünkel, W.; Poulsen, A.; Entzeroth, M. N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone deacetylase inhibitors: design, synthesis, SAR studies, and in vivo antitumor activity. Bioorg. Med. Chem. Lett., 2009, 19(5), 1403-1408.
[http://dx.doi.org/10.1016/j.bmcl.2009.01.041] [PMID: 19181524]
[63]
Bressi, J.C.; de Jong, R.; Wu, Y.; Jennings, A.J.; Brown, J.W.; O’Connell, S.; Tari, L.W.; Skene, R.J.; Vu, P.; Navre, M.; Cao, X.; Gangloff, A.R. Benzimidazole and imidazole inhibitors of histone deacetylases: synthesis and biological activity. Bioorg. Med. Chem. Lett., 2010, 20(10), 3138-3141.
[http://dx.doi.org/10.1016/j.bmcl.2010.03.092] [PMID: 20392637]
[64]
Folkman, J. Fundamental concepts of the angiogenic process. Curr. Mol. Med., 2003, 3(7), 643-651.
[http://dx.doi.org/10.2174/1566524033479465] [PMID: 14601638]
[65]
Kerbel, R.S. Tumor angiogenesis: past, present and the near future. Carcinogenesis, 2000, 21(3), 505-515.
[http://dx.doi.org/10.1093/carcin/21.3.505] [PMID: 10688871]
[66]
Carmeliet, P. Angiogenesis in health and disease. Nat. Med., 2003, 9(6), 653-660.
[http://dx.doi.org/10.1038/nm0603-653] [PMID: 12778163]
[67]
McBride, C.M.; Renhowe, P.A.; Heise, C.; Jansen, J.M.; Lapointe, G.; Ma, S.; Piñeda, R.; Vora, J.; Wiesmann, M.; Shafer, C.M. Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg. Med. Chem. Lett., 2006, 16(13), 3595-3599.
[http://dx.doi.org/10.1016/j.bmcl.2006.03.069] [PMID: 16603352]
[68]
McBride, C.M.; Renhowe, P.A.; Gesner, T.G.; Jansen, J.M.; Lin, J.; Ma, S.; Zhou, Y.; Shafer, C.M. 3-Benzimidazol-2-yl-1H-indazoles as potent c-ABL inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(14), 3789-3792.
[http://dx.doi.org/10.1016/j.bmcl.2006.04.043] [PMID: 16678414]
[69]
Chung, K-H.; Hong, S-Y.; You, H-J.; Park, R-E.; Ryu, C-K. Synthesis and biological evaluation of 5-arylamino-1H-benzo[d]imidazole-4,7-diones as inhibitor of endothelial cell proliferation. Bioorg. Med. Chem., 2006, 14(17), 5795-5801.
[http://dx.doi.org/10.1016/j.bmc.2006.05.059] [PMID: 16784869]
[70]
Liu, X.; Fan, P.; Wang, S.; Wu, Z.Y. Expression of vascular endothelial cell growth factor and its receptor mRNA in breast cancer tissues. Zhonghua Wai Ke Za Zhi, 2003, 41(2), 119-121.
[PMID: 12783674]
[71]
Mostafa, A.S.; Gomaa, R.M.; Elmorsy, M.A. Design and synthesis of 2-phenyl benzimidazole derivatives as VEGFR-2 inhibitors with anti-breast cancer activity. Chem. Biol. Drug Des., 2019, 93(4), 454-463.
[http://dx.doi.org/10.1111/cbdd.13433] [PMID: 30393973]
[72]
Hori, A.; Imaeda, Y.; Kubo, K.; Kusaka, M. Novel benzimidazole derivatives selectively inhibit endothelial cell growth and suppress angiogenesis in vitro and in vivo. Cancer Lett., 2002, 183(1), 53-60.
[http://dx.doi.org/10.1016/S0304-3835(02)00110-6] [PMID: 12049814]
[73]
Shi, L.; Wu, T.T.; Wang, Z.; Xue, J.Y.; Xu, Y.G. Discovery of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives as novel VEGFR-2 kinase inhibitors. Eur. J. Med. Chem., 2014, 84, 698-707.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.071] [PMID: 25064347]
[74]
Temirak, A.; Shaker, Y.M.; Ragab, F.A.; Ali, M.M.; Ali, H.I.; El Diwani, H.I.; Part, I.; Part, I. Synthesis, biological evaluation and docking studies of new 2-furylbenzimidazoles as antiangiogenic agents. Eur. J. Med. Chem., 2014, 87, 868-880.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.063] [PMID: 24576797]
[75]
Abdullaziz, M.A.; Abdel-Mohsen, H.T.; El Kerdawy, A.M.; Ragab, F.A.F.; Ali, M.M.; Abu-Bakr, S.M.; Girgis, A.S.; El Diwani, H.I. Design, synthesis, molecular docking and cytotoxic evaluation of novel 2-furybenzimidazoles as VEGFR-2 inhibitors. Eur. J. Med. Chem., 2017, 136, 315-329.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.068] [PMID: 28505536]
[76]
Ashok, A.; Thanukrishnan, K.; Bhojya Naik, H.S.; Maridu, R. Novel aryl-modified benzoylamino-N-(5,6-dimethoxy-1H-benzoimidazol-2-yl)-heteroa-mides as potent inhibitors of vascular endothelial growth factor receptors 1 and 2. J. Heterocycl. Chem., 2017, 54, 1949-1956.
[http://dx.doi.org/10.1002/jhet.2791]
[77]
Marco-Contelles, J.; Soriano, E. The medicinal chemistry of hybrid-based drugs targeting multiple sites of action. Curr. Top. Med. Chem., 2011, 11(22), 2714-2715.
[http://dx.doi.org/10.2174/156802611798184382] [PMID: 22039874]
[78]
Ibrahim, H.A.; Awadallah, F.M.; Refaat, H.M.; Amin, K.M. Design, synthesis and molecular modeling study for some new 2-substituted benzimidazoles as dual inhibitors for VEGFR-2 and c-Met. Future Med. Chem., 2018, 10(5), 493-509.
[http://dx.doi.org/10.4155/fmc-2017-0174] [PMID: 29431476]
[79]
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]
[80]
Zhong, H.; Tran, L.M.; Stang, J.L. Induced-fit docking studies of the active and inactive states of protein tyrosine kinases. J. Mol. Graph. Model., 2009, 28(4), 336-346.
[http://dx.doi.org/10.1016/j.jmgm.2009.08.012] [PMID: 19767223]
[81]
Kaspersen, S.J.; Han, J.; Nørsett, K.G.; Rydså, L.; Kjøbli, E.; Bugge, S.; Bjørkøy, G.; Sundby, E.; Hoff, B.H. Identification of new 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4-amines as highly potent EGFR-TK inhibitors with Src-family activity. Eur. J. Pharm. Sci., 2014, 59, 69-82.
[http://dx.doi.org/10.1016/j.ejps.2014.04.011] [PMID: 24769040]
[82]
Das, D.; Xie, L.; Wang, J.; Shi, J.; Hong, J. In vivo efficacy studies of novel quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors, in lung cancer xenografts (NCI-H1975) mice models. Bioorg. Chem., 2020, 99103790
[http://dx.doi.org/10.1016/j.bioorg.2020.103790] [PMID: 32279037]
[83]
Çelik, İ.; Ayhan-Kılcıgil, G.; Guven, B.; Kara, Z.; Gurkan-Alp, A.S.; Karayel, A.; Onay-Besikci, A. Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors. Eur. J. Med. Chem., 2019, 173, 240-249.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.012] [PMID: 31009910]
[84]
Yadav, S.; Sinha, D.; Singh, S.K.; Singh, V.K. Novel benzimidazole analogs as inhibitors of EGFR tyrosine kinase. Chem. Biol. Drug Des., 2012, 80(4), 625-630.
[http://dx.doi.org/10.1111/j.1747-0285.2012.01407.x] [PMID: 22564276]
[85]
Chhajed, S.S.; Sonawane, S.S.; Upasani, C.D.; Kshirsagar, S.J.; Gupta, P.P. Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent. Comput. Biol. Chem., 2016, 61, 138-144.
[http://dx.doi.org/10.1016/j.compbiolchem.2016.02.001] [PMID: 26878127]
[86]
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]
[87]
Akhtar, M.J.; Khan, A.A.; Ali, Z.; Dewangan, R.P.; Rafi, M.; Hassan, M.Q.; Akhtar, M.S.; Siddiqui, A.A.; Partap, S.; Pasha, S.; Yar, M.S. Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors. Bioorg. Chem., 2018, 78, 158-169.
[http://dx.doi.org/10.1016/j.bioorg.2018.03.002] [PMID: 29571113]
[88]
Srour, A.M.; Ahmed, N.S.; Abd El-Karim, S.S.; Anwar, M.M.; El-Hallouty, S.M. Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors. Bioorg. Med. Chem., 2020, 28(18)115657
[http://dx.doi.org/10.1016/j.bmc.2020.115657] [PMID: 32828424]
[89]
Gryshchenko, A.A.; Tarnavskiy, S.S.; Levchenko, K.V.; Bdzhola, V.G.; Volynets, G.P.; Golub, A.G.; Ruban, T.P.; Vygranenko, K.V.; Lukash, L.L.; Yarmoluk, S.M. Design, synthesis and biological evaluation of 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones as inhibitors of protein kinase FGFR1. Bioorg. Med. Chem., 2016, 24(9), 2053-2059.
[http://dx.doi.org/10.1016/j.bmc.2016.03.036] [PMID: 27017541]
[90]
Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature, 1993, 362(6423), 801-809.
[http://dx.doi.org/10.1038/362801a0] [PMID: 8479518]
[91]
Ferns, G.A.; Raines, E.W.; Sprugel, K.H.; Motani, A.S.; Reidy, M.A.; Ross, R. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science, 1991, 253(5024), 1129-1132.
[http://dx.doi.org/10.1126/science.1653454] [PMID: 1653454]
[92]
Hong, S-Y.; Chung, K-H.; You, H-J.; Choi, I.H.; Chae, M.J.; Han, J-Y.; Jung, O-J.; Kang, S-J.; Ryu, C-K. Synthesis and biological evaluation of benzimidazole-4,7-diones that inhibit vascular smooth muscle cell proliferation. Bioorg. Med. Chem. Lett., 2004, 14(13), 3563-3566.
[http://dx.doi.org/10.1016/j.bmcl.2004.04.051] [PMID: 15177474]
[93]
Velaparthi, U.; Liu, P.; Balasubramanian, B.; Carboni, J.; Attar, R.; Gottardis, M.; Li, A.; Greer, A.; Zoeckler, M.; Wittman, M.D.; Vyas, D. Imidazole moiety replacements in the 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one inhibitors of insulin-like growth factor receptor-1 (IGF-1R) to improve cytochrome P450 profile. Bioorg. Med. Chem. Lett., 2007, 17(11), 3072-3076.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.048] [PMID: 17398093]
[94]
Wittman, M.; Carboni, J.; Attar, R.; Balasubramanian, B.; Balimane, P.; Brassil, P.; Beaulieu, F.; Chang, C.; Clarke, W.; Dell, J.; Eummer, J.; Frennesson, D.; Gottardis, M.; Greer, A.; Hansel, S.; Hurlburt, W.; Jacobson, B.; Krishnananthan, S.; Lee, F.Y.; Li, A.; Lin, T.A.; Liu, P.; Ouellet, C.; Sang, X.; Saulnier, M.G.; Stoffan, K.; Sun, Y.; Velaparthi, U.; Wong, H.; Yang, Z.; Zimmermann, K.; Zoeckler, M.; Vyas, D. Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J. Med. Chem., 2005, 48(18), 5639-5643.
[http://dx.doi.org/10.1021/jm050392q] [PMID: 16134929]
[95]
Wittman, M.D.; Balasubramanian, B.; Stoffan, K.; Velaparthi, U.; Liu, P.; Krishnanathan, S.; Carboni, J.; Li, A.; Greer, A.; Attar, R.; Gottardis, M.; Chang, C.; Jacobson, B.; Sun, Y.; Hansel, S.; Zoeckler, M.; Vyas, D.M. Novel 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase. Bioorg. Med. Chem. Lett., 2007, 17(4), 974-977.
[http://dx.doi.org/10.1016/j.bmcl.2006.11.041] [PMID: 17187980]
[96]
Velaparthi, U.; Saulnier, M.G.; Wittman, M.D.; Liu, P.; Frennesson, D.B.; Zimmermann, K.; Carboni, J.M.; Gottardis, M.; Li, A.; Greer, A.; Clarke, W.; Yang, Z.; Menard, K.; Lee, F.Y.; Trainor, G.; Vyas, D. Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one. Bioorg. Med. Chem. Lett., 2010, 20(10), 3182-3185.
[http://dx.doi.org/10.1016/j.bmcl.2010.03.057] [PMID: 20399649]
[97]
Zimmermann, K.; Wittman, M.D.; Saulnier, M.G.; Velaparthi, U.; Sang, X.; Frennesson, D.B.; Struzynski, C.; Seitz, S.P.; He, L.; Carboni, J.M.; Li, A.; Greer, A.F.; Gottardis, M.; Attar, R.M.; Yang, Z.; Balimane, P.; Discenza, L.N.; Lee, F.Y.; Sinz, M.; Kim, S.; Vyas, D. SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(5), 1744-1748.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.087] [PMID: 20153189]
[98]
Velaparthi, U.; Wittman, M.; Liu, P.; Stoffan, K.; Zimmermann, K.; Sang, X.; Carboni, J.; Li, A.; Attar, R.; Gottardis, M.; Greer, A.; Chang, C.Y.; Jacobsen, B.L.; Sack, J.S.; Sun, Y.; Langley, D.R.; Balasubramanian, B.; Vyas, D. Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R). Bioorg. Med. Chem. Lett., 2007, 17(8), 2317-2321.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.102] [PMID: 17317169]
[99]
Katritzky, A.R.; Dobchev, D.A.; Fara, D.C.; Karelson, M. QSAR studies on 1-phenylbenzimidazoles as inhibitors of the platelet-derived growth factor. Bioorg. Med. Chem., 2005, 13(24), 6598-6608.
[http://dx.doi.org/10.1016/j.bmc.2005.06.067] [PMID: 16230017]
[100]
Palmer, B.D.; Smaill, J.B.; Boyd, M.; Boschelli, D.H.; Doherty, A.M.; Hamby, J.M.; Khatana, S.S.; Kramer, J.B.; Kraker, A.J.; Panek, R.L.; Lu, G.H.; Dahring, T.K.; Winters, R.T.; Showalter, H.D.; Denny, W.A. Structure-activity relationships for 1-phenylbenzimidazoles as selective ATP site inhibitors of the platelet-derived growth factor receptor. J. Med. Chem., 1998, 41(27), 5457-5465.
[http://dx.doi.org/10.1021/jm9804681] [PMID: 9876115]
[101]
Palmer, B.D.; Kraker, A.J.; Hartl, B.G.; Panopoulos, A.D.; Panek, R.L.; Batley, B.L.; Lu, G.H.; Trumpp-Kallmeyer, S.; Showalter, H.D.; Denny, W.A. Structure-activity relationships for 5-substituted 1-phenylbenzimi-dazoles as selective inhibitors of the platelet-derived growth factor receptor. J. Med. Chem., 1999, 42(13), 2373-2382.
[http://dx.doi.org/10.1021/jm980658b] [PMID: 10395478]
[102]
Zhong, C.; He, J.; Xue, C.; Li, Y. A QSAR study on inhibitory activities of 1-phenylbenzimidazoles against the platelet-derived growth factor receptor. Bioorg. Med. Chem., 2004, 12(15), 4009-4015.
[http://dx.doi.org/10.1016/j.bmc.2004.06.002] [PMID: 15246078]
[103]
Zien, P.; Duncan, J.S.; Skierski, J.; Bretner, M.; Litchfield, D.W.; Shugar, D. Tetrabromobenzotriazole (TBBt) and tetrabromobenzimidazole (TBBz) as selective inhibitors of protein kinase CK2: evaluation of their effects on cells and different molecular forms of human CK2. Biochim. Biophys. Acta, 2005, 1754(1-2), 271-280.
[http://dx.doi.org/10.1016/j.bbapap.2005.07.039] [PMID: 16203192]
[104]
Noy, P.; Sawasdichai, A.; Jayaraman, P-S.; Gaston, K. Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival. Nucleic Acids Res., 2012, 40(18), 9008-9020.
[http://dx.doi.org/10.1093/nar/gks687] [PMID: 22844093]
[105]
Ni, Z-J.; Barsanti, P.; Brammeier, N.; Diebes, A.; Poon, D.J.; Ng, S.; Pecchi, S.; Pfister, K.; Renhowe, P.A.; Ramurthy, S.; Wagman, A.S.; Bussiere, D.E.; Le, V.; Zhou, Y.; Jansen, J.M.; Ma, S.; Gesner, T.G. 4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(12), 3121-3124.
[http://dx.doi.org/10.1016/j.bmcl.2006.03.059] [PMID: 16603354]
[106]
Najda-Bernatowicz, A.; Łebska, M.; Orzeszko, A.; Kopańska, K.; Krzywińska, E.; Muszyńska, G.; Bretner, M. Synthesis of new analogs of benzotriazole, benzimidazole and phthalimide--potential inhibitors of human protein kinase CK2. Bioorg. Med. Chem., 2009, 17(4), 1573-1578.
[http://dx.doi.org/10.1016/j.bmc.2008.12.071] [PMID: 19168362]
[107]
Hua, Z.; Huang, X.; Bregman, H.; Chakka, N.; DiMauro, E.F.; Doherty, E.M.; Goldstein, J.; Gunaydin, H.; Huang, H.; Mercede, S.; Newcomb, J.; Patel, V.F.; Turci, S.M.; Yan, J.; Wilson, C.; Martin, M.W. 2-Phenylamino-6-cyano-1H-benzimidazole-based isoform selective casein kinase 1 gamma (CK1γ) inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(17), 5392-5395.
[http://dx.doi.org/10.1016/j.bmcl.2012.07.046] [PMID: 22877629]
[108]
Pagano, M.A.; Andrzejewska, M.; Ruzzene, M.; Sarno, S.; Cesaro, L.; Bain, J.; Elliott, M.; Meggio, F.; Kazimierczuk, Z.; Pinna, L.A. Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J. Med. Chem., 2004, 47(25), 6239-6247.
[http://dx.doi.org/10.1021/jm049854a] [PMID: 15566294]
[109]
Pagano, M.A.; Meggio, F.; Ruzzene, M.; Andrzejewska, M.; Kazimierczuk, Z.; Pinna, L.A. 2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole: a novel powerful and selective inhibitor of protein kinase CK2. Biochem. Biophys. Res. Commun., 2004, 321(4), 1040-1044.
[http://dx.doi.org/10.1016/j.bbrc.2004.07.067] [PMID: 15358133]
[110]
Bain, J.; Plater, L.; Elliott, M.; Shpiro, N.; Hastie, C.J.; McLauchlan, H.; Klevernic, I.; Arthur, J.S.; Alessi, D.R.; Cohen, P. The selectivity of protein kinase inhibitors: a further update. Biochem. J., 2007, 408(3), 297-315.
[http://dx.doi.org/10.1042/BJ20070797] [PMID: 17850214]
[111]
Battistutta, R.; Mazzorana, M.; Cendron, L.; Bortolato, A.; Sarno, S.; Kazimierczuk, Z.; Zanotti, G.; Moro, S.; Pinna, L.A. The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules. ChemBioChem, 2007, 8(15), 1804-1809.
[http://dx.doi.org/10.1002/cbic.200700307] [PMID: 17768728]
[112]
Battistutta, R.; De Moliner, E.; Sarno, S.; Zanotti, G.; Pinna, L.A. Structural features underlying selective inhibition of protein kinase CK2 by ATP site-directed tetrabromo-2-benzotriazole. Protein Sci., 2001, 10(11), 2200-2206.
[http://dx.doi.org/10.1110/ps.19601] [PMID: 11604527]
[113]
Battistutta, R.; Mazzorana, M.; Sarno, S.; Kazimierczuk, Z.; Zanotti, G.; Pinna, L.A. Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole. Chem. Biol., 2005, 12(11), 1211-1219.
[http://dx.doi.org/10.1016/j.chembiol.2005.08.015] [PMID: 16298300]
[114]
Pagano, M.A.; Bain, J.; Kazimierczuk, Z.; Sarno, S.; Ruzzene, M.; Di Maira, G.; Elliott, M.; Orzeszko, A.; Cozza, G.; Meggio, F.; Pinna, L.A. The selectivity of inhibitors of protein kinase CK2: an update. Biochem. J., 2008, 415(3), 353-365.
[http://dx.doi.org/10.1042/BJ20080309] [PMID: 18588507]
[115]
Gianoncelli, A.; Cozza, G.; Orzeszko, A.; Meggio, F.; Kazimierczuk, Z.; Pinna, L.A. Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2. Bioorg. Med. Chem., 2009, 17(20), 7281-7289.
[http://dx.doi.org/10.1016/j.bmc.2009.08.047] [PMID: 19748274]
[116]
Janeczko, M.; Orzeszko, A.; Kazimierczuk, Z.; Szyszka, R.; Baier, A. CK2α and CK2α′ subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur. J. Med. Chem., 2012, 47(1), 345-350.
[http://dx.doi.org/10.1016/j.ejmech.2011.11.002] [PMID: 22115617]
[117]
Schneider, C.C.; Kartarius, S.; Montenarh, M.; Orzeszko, A.; Kazimierczuk, Z. Modified tetrahalogenated benzimidazoles with CK2 inhibitory activity are active against human prostate cancer cells LNCaP in vitro. Bioorg. Med. Chem., 2012, 20(14), 4390-4396.
[http://dx.doi.org/10.1016/j.bmc.2012.05.038] [PMID: 22698781]
[118]
Arienti, K.L.; Brunmark, A.; Axe, F.U.; McClure, K.; Lee, A.; Blevitt, J.; Neff, D.K.; Huang, L.; Crawford, S.; Pandit, C.R.; Karlsson, L.; Breitenbucher, J.G. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J. Med. Chem., 2005, 48(6), 1873-1885.
[http://dx.doi.org/10.1021/jm0495935] [PMID: 15771432]
[119]
McClure, K.J.; Huang, L.; Arienti, K.L.; Axe, F.U.; Brunmark, A.; Blevitt, J.; Breitenbucher, J.G. Novel non-benzimidazole chk2 kinase inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(7), 1924-1928.
[http://dx.doi.org/10.1016/j.bmcl.2005.12.096] [PMID: 16442290]
[120]
Neff, D.K.; Lee-Dutra, A.; Blevitt, J.M.; Axe, F.U.; Hack, M.D.; Buma, J.C.; Rynberg, R.; Brunmark, A.; Karlsson, L.; Breitenbucher, J.G. 2-Aryl benzimidazoles featuring alkyl-linked pendant alcohols and amines as inhibitors of checkpoint kinase chk2. Bioorg. Med. Chem. Lett., 2007, 17(23), 6467-6471.
[http://dx.doi.org/10.1016/j.bmcl.2007.09.098] [PMID: 17937984]
[121]
Koca, İ.; Özgür, A.; Coşkun, K.A.; Tutar, Y. Synthesis and anticancer activity of acyl thioureas bearing pyrazole moiety. Bioorg. Med. Chem., 2013, 21(13), 3859-3865.
[http://dx.doi.org/10.1016/j.bmc.2013.04.021] [PMID: 23664495]
[122]
Reddy, T.S.; Kulhari, H.; Reddy, V.G.; Bansal, V.; Kamal, A.; Shukla, R. Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents. Eur. J. Med. Chem., 2015, 101, 790-805.
[http://dx.doi.org/10.1016/j.ejmech.2015.07.031] [PMID: 26231080]
[123]
Galal, S.A.; Abdelsamie, A.S.; Shouman, S.A.; Attia, Y.M.; Ali, H.I.; Tabll, A.; El-Shenawy, R.; El Abd, Y.S.; Ali, M.M.; Mahmoud, A.E.; Abdel-Halim, A.H.; Fyiad, A.A.; Girgis, A.S.; El-Diwani, H.I.; Part, I. Design, synthesis and biological evaluation of novel pyrazole-benzimidazole conjugates as checkpoint kinase 2 (chk2) inhibitors with studying their activities alone and in combination with genotoxic drugs. Eur. J. Med. Chem., 2017, 134, 392-405.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.090] [PMID: 28433679]
[124]
Galal, S.A.; Khairat, S.H.M.; Ali, H.I.; Shouman, S.A.; Attia, Y.M.; Ali, M.M.; Mahmoud, A.E.; Abdel-Halim, A.H.; Fyiad, A.A.; Tabll, A.; El-Shenawy, R.; El Abd, Y.S.; Ramdan, R.; El Diwani, H.I.; Part, I.I. New candidates of pyrazole-benzimidazole conjugates as checkpoint kinase 2 (chk2) inhibitors. Eur. J. Med. Chem., 2018, 144, 859-873.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.023] [PMID: 29316526]
[125]
Galal, S.A.; Khattab, M.; Shouman, S.A.; Ramadan, R.; Kandil, O.M.; Kandil, O.M.; Tabll, A.; El Abd, Y.S.; El-Shenawy, R.; Attia, Y.M.; El-Rashedy, A.A.; El Diwani, H.I. Part III: novel checkpoint kinase 2 (chk2) inhibitors; design, synthesis and biological evaluation of pyrimidine-benzimidazole conjugates. Eur. J. Med. Chem., 2018, 146, 687-708.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.072] [PMID: 29407991]
[126]
Yaguchi, S.; Fukui, Y.; Koshimizu, I.; Yoshimi, H.; Matsuno, T.; Gouda, H.; Hirono, S.; Yamazaki, K.; Yamori, T. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J. Natl. Cancer Inst., 2006, 98(8), 545-556.
[http://dx.doi.org/10.1093/jnci/djj133] [PMID: 16622124]
[127]
Kong, D.; Yamori, T. ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms. Cancer Sci., 2007, 98(10), 1638-1642.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00580.x] [PMID: 17711503]
[128]
Kong, D.; Yaguchi, S.; Yamori, T. Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase. Biol. Pharm. Bull., 2009, 32(2), 297-300.
[http://dx.doi.org/10.1248/bpb.32.297] [PMID: 19182393]
[129]
Kong, D.X.; Yamori, T. ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system. Acta Pharmacol. Sin., 2010, 31(9), 1189-1197.
[http://dx.doi.org/10.1038/aps.2010.150] [PMID: 20729870]
[130]
Dan, S.; Yoshimi, H.; Okamura, M.; Mukai, Y.; Yamori, T. Inhibition of PI3K by ZSTK474 suppressed tumor growth not via apoptosis but G0/G1 arrest. Biochem. Biophys. Res. Commun., 2009, 379(1), 104-109.
[http://dx.doi.org/10.1016/j.bbrc.2008.12.015] [PMID: 19094964]
[131]
Rewcastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Frederick, R.; Denny, W.A.; Baguley, B.C.; Kestell, P.; Singh, R.; Kendall, J.D.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Buchanan, C.M.; Jamieson, S.M.; Shepherd, P.R. Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474). J. Med. Chem., 2011, 54(20), 7105-7126.
[http://dx.doi.org/10.1021/jm200688y] [PMID: 21882832]
[132]
Gamage, S.A.; Giddens, A.C.; Tsang, K.Y.; Flanagan, J.U.; Kendall, J.D.; Lee, W.J.; Baguley, B.C.; Buchanan, C.M.; Jamieson, S.M.F.; Shepherd, P.R.; Denny, W.A.; Rewcastle, G.W. Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474. Bioorg. Med. Chem., 2017, 25(20), 5859-5874.
[http://dx.doi.org/10.1016/j.bmc.2017.09.025] [PMID: 28958845]
[133]
Giddens, A.C.; Gamage, S.A.; Kendall, J.D.; Lee, W.J.; Baguley, B.C.; Buchanan, C.M.; Jamieson, S.M.F.; Dickson, J.M.J.; Shepherd, P.R.; Denny, W.A.; Rewcastle, G.W. Synthesis and biological evaluation of solubilized sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474. Bioorg. Med. Chem., 2019, 27(8), 1529-1545.
[http://dx.doi.org/10.1016/j.bmc.2019.02.050] [PMID: 30850264]
[134]
Fei, B.L.; Tu, S.; Wei, Z.; Wang, P.; Qiao, C.; Chen, Z.F. Optically pure chiral copper(II) complexes of rosin derivative as attractive anticancer agents with potential anti-metastatic and anti-angiogenic activities. Eur. J. Med. Chem., 2019, 176, 175-186.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.030] [PMID: 31103898]
[135]
Yang, Y.Q.; Chen, H.; Liu, Q.S.; Sun, Y.; Gu, W. Synthesis and anticancer evaluation of novel 1H-benzo[d]imidazole derivatives of dehydroabietic acid as PI3Kα inhibitors. Bioorg. Chem., 2020, 100103845
[http://dx.doi.org/10.1016/j.bioorg.2020.103845] [PMID: 32344183]
[136]
Della Corte, C.M.; Viscardi, G.; Di Liello, R.; Fasano, M.; Martinelli, E.; Troiani, T.; Ciardiello, F.; Morgillo, F. Role and targeting of anaplastic lymphoma kinase in cancer. Mol. Cancer, 2018, 17(1), 30.
[http://dx.doi.org/10.1186/s12943-018-0776-2] [PMID: 29455642]
[137]
Lewis, R.T.; Bode, C.M.; Choquette, D.M.; Potashman, M.; Romero, K.; Stellwagen, J.C.; Teffera, Y.; Moore, E.; Whittington, D.A.; Chen, H.; Epstein, L.F.; Emkey, R.; Andrews, P.S.; Yu, V.L.; Saffran, D.C.; Xu, M.; Drew, A.; Merkel, P.; Szilvassy, S.; Brake, R.L. The discovery and optimization of a novel class of potent, selective, and orally bioavailable Anaplastic Lymphoma Kinase (ALK) inhibitors with potential utility for the treatment of cancer. J. Med. Chem., 2012, 55(14), 6523-6540.
[http://dx.doi.org/10.1021/jm3005866] [PMID: 22734674]
[138]
Zhong, M.; Bui, M.; Shen, W.; Baskaran, S.; Allen, D.A.; Elling, R.A.; Flanagan, W.M.; Fung, A.D.; Hanan, E.J.; Harris, S.O.; Heumann, S.A.; Hoch, U.; Ivy, S.N.; Jacobs, J.W.; Lam, S.; Lee, H.; McDowell, R.S.; Oslob, J.D.; Purkey, H.E.; Romanowski, M.J.; Silverman, J.A.; Tangonan, B.T.; Taverna, P.; Yang, W.; Yoburn, J.C.; Yu, C.H.; Zimmerman, K.M.; O’Brien, T.; Lew, W. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(17), 5158-5161.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.016] [PMID: 19646866]
[139]
Yang, L.; Jiang, C.; Liu, F.; You, Q.D.; Wu, W.T. Cloning, enzyme characterization of recombinant human Eg5 and the development of a new inhibitor. Biol. Pharm. Bull., 2008, 31(7), 1397-1402.
[http://dx.doi.org/10.1248/bpb.31.1397] [PMID: 18591782]
[140]
Garuti, L.; Roberti, M.; Bottegoni, G. Small molecule aurora kinases inhibitors. Curr. Med. Chem., 2009, 16(16), 1949-1963.
[http://dx.doi.org/10.2174/092986709788682227] [PMID: 19519375]
[141]
Fu, R.G.; You, Q.D.; Yang, L.; Wu, W.T.; Jiang, C.; Xu, X.L. Design, synthesis and bioevaluation of dihydropyrazolo[3,4-b]pyridine and benzo[4,5]-imidazo[1,2-a]pyrimidine compounds as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents. Bioorg. Med. Chem., 2010, 18(22), 8035-8043.
[http://dx.doi.org/10.1016/j.bmc.2010.09.020] [PMID: 20934346]
[142]
Abd El-All, A.S.; Magd-El-Din, A.A.; Ragab, F.A.; ElHefnawi, M.; Abdalla, M.M.; Galal, S.A.; El-Rashedy, A.A. New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities. Arch. Pharm. (Weinheim), 2015, 348(7), 475-486.
[http://dx.doi.org/10.1002/ardp.201400441] [PMID: 25900113]
[143]
Determann, R.; Dreher, J.; Baumann, K.; Preu, L.; Jones, P.G.; Totzke, F.; Schächtele, C.; Kubbutat, M.H.; Kunick, C. 2-Anilino-4-(benzimidazol-2-yl)pyrimidines--a multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines. Eur. J. Med. Chem., 2012, 53, 254-263.
[http://dx.doi.org/10.1016/j.ejmech.2012.04.007] [PMID: 22560627]
[144]
Sharma, A.; Luxami, V.; Paul, K. Synthesis, single crystal and antitumor activities of benzimidazole-quinazoline hybrids. Bioorg. Med. Chem. Lett., 2013, 23(11), 3288-3294.
[http://dx.doi.org/10.1016/j.bmcl.2013.03.107] [PMID: 23611732]
[145]
Sharma, A.; Luxami, V.; Saxena, S.; Paul, K. Benzimidazole-based quinazolines: In vitro evaluation, quantitative structure–activity relationship, and molecular modeling as Aurora Kinase inhibitors. Arch. Pharm. (Weinheim), 2016, 349(3), 193-201.
[http://dx.doi.org/10.1002/ardp.201500281] [PMID: 26773437]
[146]
Sharma, A.; Luxami, V.; Paul, K. Purine-benzimidazole hybrids: synthesis, single crystal determination and in vitro evaluation of antitumor activities. Eur. J. Med. Chem., 2015, 93, 414-422.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.036] [PMID: 25728022]
[147]
Fan, C.; Zhong, T.; Yang, H.; Yang, Y.; Wang, D.; Yang, X.; Xu, Y.; Fan, Y. Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imi-dazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition. Eur. J. Med. Chem., 2020, 190112108
[http://dx.doi.org/10.1016/j.ejmech.2020.112108] [PMID: 32058239]
[148]
Coban, G.; Zencir, S.; Zupkó, I.; Réthy, B.; Gunes, H.S.; Topcu, Z. Synthesis and biological activity evaluation of 1H-benzimidazoles via mammalian DNA topoisomerase I and cytostaticity assays. Eur. J. Med. Chem., 2009, 44(5), 2280-2285.
[http://dx.doi.org/10.1016/j.ejmech.2008.06.018] [PMID: 18692939]
[149]
Champoux, J.J. Mechanistic Aspects of Type-I Topoisomerases; Cold Spring Harbor Laboratory Press: NewYork, 1990.
[150]
Nitiss, J.L. Investigating the biological functions of DNA topoisomerases in eukaryotic cells. Biochim. Biophys. Acta, 1998, 1400(1-3), 63-81.
[http://dx.doi.org/10.1016/S0167-4781(98)00128-6] [PMID: 9748506]
[151]
McHugh, M.M.; Woynarowski, J.M.; Sigmund, R.D.; Beerman, T.A. Effect of minor groove binding drugs on mammalian topoisomerase I activity. Biochem. Pharmacol., 1989, 38(14), 2323-2328.
[http://dx.doi.org/10.1016/0006-2952(89)90472-3] [PMID: 2473754]
[152]
Kühholzer, B.; Prather, R.S. Synchronization of porcine fetal fibroblast cells with topoisomerase-inhibitor hoechst 33342. Anim. Reprod. Sci., 2001, 66(1-2), 109-116.
[http://dx.doi.org/10.1016/S0378-4320(01)00088-4] [PMID: 11343846]
[153]
Nitiss, J.L. DNA topoisomerase II and its growing repertoire of biological functions. Nat. Rev. Cancer, 2009, 9(5), 327-337.
[http://dx.doi.org/10.1038/nrc2608] [PMID: 19377505]
[154]
Yuan, Z.; Chen, S.; Chen, C.; Chen, J.; Chen, C.; Dai, Q.; Gao, C.; Jiang, Y. Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy. Eur. J. Med. Chem., 2017, 138, 1135-1146.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.050] [PMID: 28763648]
[155]
Mousavi, S.M.; Zarei, M.; Hashemi, S.A.; Babapoor, A.; Amani, A.M. A conceptual review of rhodanine: current applications of antiviral drugs, anticancer and antimicrobial activities. Artif. cell Nanomed.B., 2019, 47, 1132-1148.
[156]
Li, P.; Zhang, W.; Jiang, H.; Li, Y.; Dong, C.; Chen, H.; Zhang, K.; Du, Z. Design, synthesis and biological evaluation of benzimidazole-rhodanine conjugates as potent topoisomerase II inhibitors. MedChemComm, 2018, 9(7), 1194-1205.
[http://dx.doi.org/10.1039/C8MD00278A] [PMID: 30109008]
[157]
Singh, I.; Luxami, V.; Paul, K. Effective synthesis of benzimidazoles-imidazo[1,2-a]pyrazine conjugates: A comparative study of mono-and bis-benzimidazoles for antitumor activity. Eur. J. Med. Chem., 2019, 180, 546-561.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.042] [PMID: 31344614]
[158]
Penning, T.D.; Zhu, G.D.; Gandhi, V.B.; Gong, J.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E.F.; Donawho, C.K.; Frost, D.J.; Bontcheva-Diaz, V.; Bouska, J.J.; Osterling, D.J.; Olson, A.M.; Marsh, K.C.; Luo, Y.; Giranda, V.L. Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J. Med. Chem., 2009, 52(2), 514-523.
[http://dx.doi.org/10.1021/jm801171j] [PMID: 19143569]
[159]
White, A.W.; Almassy, R.; Calvert, A.H.; Curtin, N.J.; Griffin, R.J.; Hostomsky, Z.; Maegley, K.; Newell, D.R.; Srinivasan, S.; Golding, B.T. Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase. J. Med. Chem., 2000, 43(22), 4084-4097.
[http://dx.doi.org/10.1021/jm000950v] [PMID: 11063605]
[160]
White, A.W.; Curtin, N.J.; Eastman, B.W.; Golding, B.T.; Hostomsky, Z.; Kyle, S.; Li, J.; Maegley, K.A.; Skalitzky, D.J.; Webber, S.E.; Yu, X.H.; Griffin, R.J. Potentiation of cytotoxic drug activity in human tumour cell lines, by amine-substituted 2-arylbenzimidazole-4-carboxamide PARP-1 inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(10), 2433-2437.
[http://dx.doi.org/10.1016/j.bmcl.2004.03.017] [PMID: 15109627]
[161]
Tong, Y.; Bouska, J.J.; Ellis, P.A.; Johnson, E.F.; Leverson, J.; Liu, X.; Marcotte, P.A.; Olson, A.M.; Osterling, D.J.; Przytulinska, M.; Rodriguez, L.E.; Shi, Y.; Soni, N.; Stavropoulos, J.; Thomas, S.; Donawho, C.K.; Frost, D.J.; Luo, Y.; Giranda, V.L.; Penning, T.D. Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents. J. Med. Chem., 2009, 52(21), 6803-6813.
[http://dx.doi.org/10.1021/jm900697r] [PMID: 19888760]
[162]
Wang, J.; Wang, X.; Li, H.; Ji, D.; Li, Y.; Xu, Y.; Zhu, Q. Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(16), 4127-4132.
[http://dx.doi.org/10.1016/j.bmcl.2016.06.045] [PMID: 27353531]
[163]
Chen, X.; Huan, X.; Liu, Q.; Wang, Y.; He, Q.; Tan, C.; Chen, Y.; Ding, J.; Xu, Y.; Miao, Z.; Yang, C. Design and synthesis of 2-(4,5,6,7-tetrahydro-thienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors. Eur. J. Med. Chem., 2018, 145, 389-403.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.018] [PMID: 29335205]
[164]
Zhang, X.; Zhang, C.; Tang, L.; Lu, K.; Zhao, H.; Wu, W.; Jiang, Y. Synthesis and biological evaluation of piperidyl benzimidazole carboxamide derivatives as potent PARP-1 inhibitors and antitumor agents. Chin. Chem. Lett., 2020, 31, 136-140.
[http://dx.doi.org/10.1016/j.cclet.2019.04.045]
[165]
Chen, C.L.; Chang, D.M.; Chen, T.C.; Lee, C.C.; Hsieh, H.H.; Huang, F.C.; Huang, K.F.; Guh, J.H.; Lin, J.J.; Huang, H.S. Structure-based design, synthesis and evaluation of novel anthra[1,2-d]imidazole-6,11-dione derivatives as telomerase inhibitors and potential for cancer polypharmacology. Eur. J. Med. Chem., 2013, 60, 29-41.
[http://dx.doi.org/10.1016/j.ejmech.2012.11.032] [PMID: 23279865]
[166]
Maji, B.; Kumar, K.; Kaulage, M.; Muniyappa, K.; Bhattacharya, S. Design and synthesis of new benzimidazole-carbazole conjugates for the stabilization of human telomeric DNA, telomerase inhibition, and their selective action on cancer cells. J. Med. Chem., 2014, 57(16), 6973-6988.
[http://dx.doi.org/10.1021/jm500427n] [PMID: 25062468]

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