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Letters in Drug Design & Discovery

Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Review Article

Review on the Discovery of New Benzimidazole Derivatives as Anticancer Agents: Synthesis and Structure-activity Relationship (2010-2022)

Author(s): Km Shabanaorcid of author, Salahuddin*orcid of author, Avijit Mazumderorcid of author, Rajnish Kumarorcid of author, Vimal Dattorcid of author, Sonakshi Tyagiorcid of author, Mohammad Shahar Yarorcid of author, Mohamed Jawed Ahsanorcid of author and Mohammad Sarafrozauthors OrcID

Volume 21, Issue 3, 2024

Published on: 03 November, 2022

Page: [451 - 479] Pages: 29

DOI: 10.2174/1570180820666221017155955

Abstract

Background: Benzimidazole (Benz-fused bicyclic ring system) is the most versatile class of heterocyclic compounds due to its numerous applications in industrial and synthetic organic chemistry because of its many biological actions. Benzimidazole analogs have been used to discover various medical problems, such as cancer, bacterial infections, fungi infections, etc. Researchers are studying nitrogencontaining hybrid heterocyclic compounds because they provide a broad range of therapeutic potential and have minimal side effects.

Objective: The current literature review emphasizes recent developments in the design of new benzimidazole derivatives as possible anticancer agents with their relationship between structure and activity, which will give insight into the future design of more active benzimidazole molecules.

Results: The present review consists of synthetic protocols for the synthesis of benzimidazole derivatives along with their pharmacological potentials and structure-activity relationship in correlation with synthetic molecules to provide a depth view of the work done on benzimidazole.

Conclusion: It would be significant for further research in developing better drug molecules representing a potent derivative of medicinal agents.

Keywords: Cancer, benzimidazole, synthesis, anticancer activity, structure-activity relationship, patents.

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Graphical Abstract

Graphical abstract illustrating key findings of the study

[1]
Birner, P.; Prager, G.; Streubel, B. Molecular pathology of cancer: How to communicate with disease. ESMO Open, 2016, 1(5), e000085.
[http://dx.doi.org/10.1136/esmoopen-2016-000085] [PMID: 27933213]
[2]
Cao, W.; Chen, H.D.; Yu, Y.W.; Li, N.; Chen, W.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J. (Engl.), 2021, 134(7), 783-791.
[http://dx.doi.org/10.1097/CM9.0000000000001474] [PMID: 33734139]
[3]
Richters, A.; Aben, K.K.H.; Kiemeney, L.A.L.M. The global burden of urinary bladder cancer: An update. World J. Urol., 2020, 38(8), 1895-1904.
[http://dx.doi.org/10.1007/s00345-019-02984-4] [PMID: 31676912]
[4]
Zhang, T.; Yang, X.; Zhou, J.; Liu, P.; Wang, H.; Li, A.; Zhou, Y. Benzodiazepine drug use and cancer risk: A dose-response meta analysis of prospective cohort studies. Oncotarget, 2017, 8(60), 102381-102391.
[http://dx.doi.org/10.18632/oncotarget.22057] [PMID: 29254253]
[5]
Ferlay, J.; Colombet, M.; Soerjomataram, I.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Cancer statistics for the year 2020: An overview. Int. J. Cancer, 2021, 149(4), 778-789.
[http://dx.doi.org/10.1002/ijc.33588] [PMID: 33818764]
[6]
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]
[7]
Saha, S.; Adhikary, A.; Bhattacharyya, P.; Das, T.; Sa, G. Death by design: Where curcumin sensitizes drug-resistant tumours. Anticancer Res., 2012, 32(7), 2567-2584.
[PMID: 22753715]
[8]
Annunziata, A.; Liberti, D.; Bedini, E.; Cucciolito, M.E.; Loreto, D.; Monti, D.M.; Merlino, A.; Ruffo, F. Square-planar vs. trigonal bipyramidal geometry in Pt(II) complexes containing triazole-based glucose ligands as potential anticancer agents. Int. J. Mol. Sci., 2021, 22(16), 8704.
[http://dx.doi.org/10.3390/ijms22168704] [PMID: 34445409]
[9]
Nall, R.R.M.C. What to Know About. Med. In: News Today; , 2000; p. 1-2.
[10]
Kamal, A.; Kashi Reddy, M.; Shaik, T.B. Rajender; Srikanth, Y.V.V.; Santhosh Reddy, V.; Bharath Kumar, G.; Kalivendi, S.V. Synthesis of terphenyl benzimidazoles as tubulin polymerization inhibitors. Eur. J. Med. Chem., 2012, 50, 9-17.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.004] [PMID: 22361684]
[11]
Hranjec, M. Starčević K.; Piantanida, I.; Kralj, M.; Marjanović M.; Hasani, M.; Westman, G.; Karminski-Zamola, G. Synthesis, antitumor evaluation and DNA binding studies of novel amidino-benzimidazolyl substituted derivatives of furyl-phenyl- and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes. Eur. J. Med. Chem., 2008, 43(12), 2877-2890.
[http://dx.doi.org/10.1016/j.ejmech.2008.02.010] [PMID: 18395297]
[12]
Shrivastava, N.; Naim, M.J.; Alam, M.J.; Nawaz, F.; Ahmed, S.; Alam, O. Benzimidazole scaffold as anticancer agent: Synthetic approaches and structure–activity relationship. Arch. Pharm. (Weinheim), 2017, 350(6), e201700040.
[http://dx.doi.org/10.1002/ardp.201700040] [PMID: 28544162]
[13]
Yadav, G.; Ganguly, S. Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review. Eur. J. Med. Chem., 2015, 97, 419-443.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.053] [PMID: 25479684]
[14]
Song, D.; Ma, S. Recent development of benzimidazole‐containing antibacterial agents. ChemMedChem, 2016, 11(7), 646-659.
[http://dx.doi.org/10.1002/cmdc.201600041] [PMID: 26970352]
[15]
Picconi, P.; Hind, C.; Jamshidi, S.; Nahar, K.; Clifford, M.; Wand, M.E.; Sutton, J.M.; Rahman, K.M. Triarylbenzimidazoles as a new class of antibacterial agents against resistant pathogenic microorganisms. J. Med. Chem., 2017, 60(14), 6045-6059.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00108] [PMID: 28650661]
[16]
Chandrika, N.T.; Shrestha, S.K.; Ngo, H.X.; Garneau-Tsodikova, S. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents. Bioorg. Med. Chem., 2016, 24(16), 3680-3686.
[http://dx.doi.org/10.1016/j.bmc.2016.06.010] [PMID: 27301676]
[17]
Morcoss, M.M.; Abdelhafez, E.S.M.N.; Ibrahem, R.A.; Abdel-Rahman, H.M.; Abdel-Aziz, M.; Abou El-Ella, D.A. Design, synthesis, mechanistic studies and in silico ADME predictions of benzimidazole derivatives as novel antifungal agents. Bioorg. Chem., 2020, 101, 103956.
[http://dx.doi.org/10.1016/j.bioorg.2020.103956] [PMID: 32512267]
[18]
Si, W.; Zhang, T.; Li, Y.; She, D.; Pan, W.; Gao, Z.; Ning, J.; Mei, X. Synthesis and biological activity of novel benzimidazole derivatives as potential antifungal agents. J. Pestic. Sci., 2015, 41(1), 15-19.
[http://dx.doi.org/10.1584/jpestics.D15-037] [PMID: 30364898]
[19]
Kanwal, A.; Ahmad, M.; Aslam, S.; Naqvi, S.A.R.; Saif, M.J. Recent advances in antiviral benzimidazole derivatives: A mini review. Pharm. Chem. J., 2019, 53(3), 179-187.
[http://dx.doi.org/10.1007/s11094-019-01976-3]
[20]
Tonelli, M.; Novelli, F.; Tasso, B.; Vazzana, I.; Sparatore, A.; Boido, V.; Sparatore, F.; La Colla, P.; Sanna, G.; Giliberti, G.; Busonera, B.; Farci, P.; Ibba, C.; Loddo, R. Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents. Bioorg. Med. Chem., 2014, 22(17), 4893-4909.
[http://dx.doi.org/10.1016/j.bmc.2014.06.043] [PMID: 25082514]
[21]
Zawawi, N.K.N.A.; Taha, M.; Ahmat, N.; Ismail, N.H.; Wadood, A.; Rahim, F. Synthesis, molecular docking studies of hybrid benzimidazole as α -glucosidase inhibitor. Bioorg. Chem., 2017, 70, 184-191.
[http://dx.doi.org/10.1016/j.bioorg.2016.12.009] [PMID: 28043716]
[22]
Asemanipoor, N.; Mohammadi-Khanaposhtani, M.; Moradi, S.; Vahidi, M.; Asadi, M.; Faramarzi, M.A.; Mahdavi, M.; Biglar, M.; Larijani, B.; Hamedifar, H.; Hajimiri, M.H. Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors. Bioorg. Chem., 2020, 95, 103482.
[http://dx.doi.org/10.1016/j.bioorg.2019.103482] [PMID: 31838286]
[23]
Zhang, Y.; Xu, J.; Li, Y.; Yao, H.; Wu, X. Design, synthesis and pharmacological evaluation of novel NO-releasing benzimidazole hybrids as potential antihypertensive candidate. Chem. Biol. Drug Des., 2015, 85(5), 541-548.
[http://dx.doi.org/10.1111/cbdd.12442] [PMID: 25283264]
[24]
Khan, M.T.; Razi, M.T.; Jan, S.U.; Mukhtiar, M.; Gul, R. IzharUllah; Hussain, A.; Hashmi, A.M.; Ahmad, M.T.; Shahwani, N.A.; Rabbani, I. Synthesis, characterization and antihypertensive activity of 2-phenyl substituted benzimidazoles. Pak. J. Pharm. Sci., 2018, 31(3), 1067-1074.
[PMID: 29731445]
[25]
Kenchappa, R.; Bodke, Y.D.; Telkar, S.; Aruna Sindhe, M. Antifungal and anthelmintic activity of novel benzofuran derivatives containing thiazolo benzimidazole nucleus: An in vitro evaluation. J. Chem. Biol., 2017, 10(1), 11-23.
[http://dx.doi.org/10.1007/s12154-016-0160-x] [PMID: 28101251]
[26]
Sethi, P.; Bansal, Y.; Bansal, G. Synthesis and PASS-assisted evaluation of coumarin–benzimidazole derivatives as potential anti-inflammatory and anthelmintic agents. Med. Chem. Res., 2018, 27(1), 61-71.
[http://dx.doi.org/10.1007/s00044-017-2036-1]
[27]
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]
[28]
Gaba, M.; Gaba, P.; Uppal, D.; Dhingra, N.; Bahia, M.S.; Silakari, O.; Mohan, C. Benzimidazole derivatives: Search for GI-friendly anti-inflammatory analgesic agents. Acta Pharm. Sin. B, 2015, 5(4), 337-342.
[http://dx.doi.org/10.1016/j.apsb.2015.05.003] [PMID: 26579464]
[29]
Veerasamy, R.; Roy, A.; Karunakaran, R.; Rajak, H. Structure–activity relationship analysis of benzimidazoles as emerging anti-inflammatory agents: An overview. Pharmaceuticals (Basel), 2021, 14(7), 663.
[http://dx.doi.org/10.3390/ph14070663] [PMID: 34358089]
[30]
Narasimhan, B.; Sharma, D.; Kumar, P. Benzimidazole: A medicinally important heterocyclic moiety. Med. Chem. Res., 2012, 21(3), 269-283.
[http://dx.doi.org/10.1007/s00044-010-9533-9]
[31]
Patel, V.M.; Patel, N.B.; Chan-Bacab, M.J.; Rivera, G. N -Mannich bases of benzimidazole as a potent antitubercular and antiprotozoal agents: Their synthesis and computational studies. Synth. Commun., 2020, 50(6), 858-878.
[http://dx.doi.org/10.1080/00397911.2020.1725057]
[32]
Pérez-Villanueva, J.; Hernández-Campos, A.; Yépez-Mulia, L.; Méndez-Cuesta, C.; Méndez-Lucio, O.; Hernández-Luis, F.; Castillo, R. Synthesis and antiprotozoal activity of novel 2-{[2-(1H-imidazol-1-yl) ethyl] sulfanyl}-1H-benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2013, 23(14), 4221-4224.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.012] [PMID: 23731944]
[33]
Siddiqui, N.; Alam, M.S.; Ali, R.; Yar, M.S.; Alam, O. Synthesis of new benzimidazole and phenylhydrazinecarbothiomide hybrids and their anticonvulsant activity. Med. Chem. Res., 2016, 25(7), 1390-1402.
[http://dx.doi.org/10.1007/s00044-016-1570-6]
[34]
Vasil’ev, P.M.; Kalitin, K.Y.; Spasov, A.A.; Grechko, O.Y.; Poroikov, V.V.; Filimonov, D.A.; Anisimova, V.A. Prediction and study of anticonvulsant properties of benzimidazole derivatives. Pharm. Chem. J., 2017, 50(12), 775-780.
[http://dx.doi.org/10.1007/s11094-017-1530-6]
[35]
Sahoo, B.M.; Banik, B.K. Mazaharunnisa; Rao, N.S.; Raju, B. Microwave-assisted green synthesis of benzimidazole derivatives and evaluation of their anticonvulsant activity. Curr. Microw. Chem., 2019, 6(1), 23-29.
[http://dx.doi.org/10.2174/2213335606666190429124745]
[36]
Cheong, J.E.; Zaffagni, M.; Chung, I.; Xu, Y.; Wang, Y.; Jernigan, F.E.; Zetter, B.R.; Sun, L. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates. Eur. J. Med. Chem., 2018, 144, 372-385.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.037] [PMID: 29288939]
[37]
Djemoui, A.; Naouri, A.; Ouahrani, M.R.; Djemoui, D.; Lahcene, S.; Lahrech, M.B.; Boukenna, L.; Albuquerque, H.M.T.; Saher, L.; Rocha, D.H.A.; Monteiro, F.L.; Helguero, L.A.; Bachari, K.; Talhi, O.; Silva, A.M.S. A step-by-step synthesis of triazole-benzimidazole-chalcone hybrids: Anticancer activity in human cells+. J. Mol. Struct., 2020, 1204, 127487.
[http://dx.doi.org/10.1016/j.molstruc.2019.127487]
[38]
Farmanzadeh, D.; Najafi, M. Benzimidazole derivatives as anticancer drugs: A theoretical investigation. J. Theor. Comput. Chem., 2015, 14(3), 1550018.
[http://dx.doi.org/10.1142/S0219633615500182]
[39]
Błaszczak-Świątkiewicz, K.; Olszewska, P.; Mikiciuk-Olasik, E. Biological approach of anticancer activity of new benzimidazole derivatives. Pharmacol. Rep., 2014, 66(1), 100-106.
[http://dx.doi.org/10.1016/j.pharep.2014.01.001] [PMID: 24905314]
[40]
Salahuddin; 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]
[41]
Sánchez-Martínez, C.; Gelbert, L.M.; Lallena, M.J.; de Dios, A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg. Med. Chem. Lett., 2015, 25(17), 3420-3435.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.100] [PMID: 26115571]
[42]
Sahyon, H.A.; El-Bindary, A.A.; Shoair, A.F.; Abdellatif, A.A. Synthesis and characterization of ruthenium(III) complex containing 2-aminomethyl benzimidazole, and its anticancer activity of in vitro and in vivo models. J. Mol. Liq., 2018, 255, 122-134.
[http://dx.doi.org/10.1016/j.molliq.2018.01.140]
[43]
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]
[44]
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]
[45]
Acar Çevik, U. Sağlık, B.N.; Ardıç, C.M.; Özkay, Y.; Atlı Ö. Synthesis and evaluation of new benzimidazole derivatives with hydrazone moiety as anticancer agents. Turk Biyokim. Derg., 2018, 43(2), 151-158.
[http://dx.doi.org/10.1515/tjb-2017-0167]
[46]
Abdelgawad, M.A.; Bakr, R.B.; Omar, H.A. Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents. Bioorg. Chem., 2017, 74, 82-90.
[http://dx.doi.org/10.1016/j.bioorg.2017.07.007] [PMID: 28772160]
[47]
Atmaca, H. İlhan, S.; Batır, M.B.; Pulat, Ç.Ç.; Güner, A.; Bektaş, H. Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies. Chem. Biol. Interact., 2020, 327, 109163.
[http://dx.doi.org/10.1016/j.cbi.2020.109163] [PMID: 32534988]
[48]
Demirayak, S.; Kayagil, I.; Yurttas, L. Microwave supported synthesis of some novel 1,3-Diarylpyrazino[1,2-a]benzimidazole derivatives and investigation of their anticancer activities. Eur. J. Med. Chem., 2011, 46(1), 411-416.
[http://dx.doi.org/10.1016/j.ejmech.2010.11.007] [PMID: 21122952]
[49]
Abdallah, A.E.; Helal, M.H.; Elakabawy, N.I. Heterocyclization, dyeing applications and anticancer evaluations of benzimidazole derivatives: Novel synthesis of thiophene, triazole and pyrimidine derivatives. Egypt. J. Chem., 2015, 58(6), 699-719.
[http://dx.doi.org/10.21608/ejchem.2015.1015]
[50]
El-Shekeil, A.; Obeid, A.O.; Al-Aghbari, S. Anticancer activity studies of some cyclic benzimidazole derivatives. Eur. J. Chem., 2012, 3(3), 356-358.
[http://dx.doi.org/10.5155/eurjchem.3.3.356-358.621]
[51]
Haoran, W.; Akhtar, W.; Nainwal, L.M.; Kaushik, S.K.; Akhter, M.; Shaquiquzzaman, M.; Alam, M.M. Synthesis and biological evaluation of benzimidazole pendant cyanopyrimidine derivatives as anticancer agents. J. Heterocycl. Chem., 2020, 57(9), jhet.4052.
[http://dx.doi.org/10.1002/jhet.4052]
[52]
Li, Y.; Tan, C.; Gao, C.; Zhang, C.; Luan, X.; Chen, X.; Liu, H.; Chen, Y.; Jiang, Y. Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and PDGFR kinase inhibitors. Bioorg. Med. Chem., 2011, 19(15), 4529-4535.
[http://dx.doi.org/10.1016/j.bmc.2011.06.022] [PMID: 21724404]
[53]
Sathyanarayana, R.; Poojary, B.; Srinivasa, S.M.; Merugumolu, V.K.; Chandrashekarappa, R.B.; Rangappa, S. In vitro, in vivo and in silico-driven identification of novel benzimidazole derivatives as anticancer and anti-inflammatory agents. J. Iranian Chem. Soc, 2021, 22, 1-7.
[54]
Yurttaş L.; Demirayak, Ş.; Çiftçi, G.A.; Yıldırım, Ş.U.; Kaplancıklı Z.A. Synthesis and biological evaluation of some 1,2-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch. Pharm. (Weinheim), 2013, 346(5), 403-414.
[http://dx.doi.org/10.1002/ardp.201200452] [PMID: 23526768]
[55]
Yadav, S.; Narasimhan, B.; Lim, S.M.; Ramasamy, K.; Vasudevan, M.; Shah, S.A.; Mathur, A. Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of benzimidazole derivatives. Egypt. J. Basic Appl. Sci., 2018, 5(1), 100-109.
[56]
Wu, L.; Jiang, Z.; Shen, J.; Yi, H.; Zhan, Y.; Sha, M.; Wang, Z.; Xue, S.; Li, Z. Design, synthesis and biological evaluation of novel benzimidazole-2-substituted phenyl or pyridine propyl ketene derivatives as antitumour agents. Eur. J. Med. Chem., 2016, 114, 328-336.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.029] [PMID: 27017265]
[57]
Sharma, P.; Thummuri, D.; Reddy, T.S.; Senwar, K.R.; Naidu, V.G.M.; Srinivasulu, G.; Bharghava, S.K.; Shankaraiah, N. New (E)-1-alkyl-1 H -benzo[d]imidazol-2-yl)methylene)indolin-2-ones: Synthesis, in vitro cytotoxicity evaluation and apoptosis inducing studies. Eur. J. Med. Chem., 2016, 122, 584-600.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.019] [PMID: 27448916]
[58]
Hranjec, M. Pavlović G.; Karminski-Zamola, G. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2-a]benzimidazoles. J. Mol. Struct., 2012, 1007, 242-251.
[http://dx.doi.org/10.1016/j.molstruc.2011.10.054]
[59]
Abdel-Aziz, H.A.; Gamal-Eldeen, A.M.; Hamdy, N.A.; Fakhr, I.M.I. Immunomodulatory and anticancer activities of some novel 2-substituted-6-bromo-3-methylthiazolo[3,2-a]benzimidazole derivatives. Arch. Pharm. (Weinheim), 2009, 342(4), 230-237.
[http://dx.doi.org/10.1002/ardp.200800189] [PMID: 19340836]
[60]
Li, S.; Zhao, J.; Yuan, B.; Wang, X.; Zhang, J.; Yue, L.; Hou, H.; Hu, J.; Chen, S. Crystal structure, DNA interaction and in vitro anticancer activity of Cu(II) and Pt(II) compounds based on benzimidazole-quinoline derivative. Polyhedron, 2020, 179, 114369.
[http://dx.doi.org/10.1016/j.poly.2020.114369]
[61]
Risley, V.A.; Henry, S.; Kosyrikhina, M.V.; Manzanares, M.R.; Payan, I.; Downer, C.D.; Hellmann, C.C.; Van Slambrouck, S.; Frolova, L.V. 4-Amino-2-aryl-3-cyano-1, 2-dihydropyrimido-[1, 2-a] benzimidazoles and their pyrimidine analogs as new anticancer agents. Chem. Heterocycl. Compd., 2014, 50(2), 185-194.
[http://dx.doi.org/10.1007/s10593-014-1460-0]
[62]
Sireesha, R.; Sreenivasulu, R.; Chandrasekhar, C.; Jadav, S.S.; Pavani, Y.; Rao, M.V.B.; Subbarao, M. Design, synthesis, anticancer evaluation and binding mode studies of benzimidazole/benzoxazole linked β-carboline derivatives. J. Mol. Struct., 2021, 1226, 129351.
[http://dx.doi.org/10.1016/j.molstruc.2020.129351]
[63]
Acar Çevik, U. Sağlık, B.N.; Korkut, B.; Özkay, Y.; Ilgın, S. Antiproliferative, cytotoxic, and apoptotic effects of new benzimidazole derivatives bearing hydrazone moiety. J. Heterocycl. Chem., 2018, 55(1), 138-148.
[http://dx.doi.org/10.1002/jhet.3016]
[64]
Refaat, H.M. Synthesis of potential anticancer derivatives of pyrido[1,2-a]benzimidazoles. Med. Chem. Res., 2012, 21(7), 1253-1260.
[http://dx.doi.org/10.1007/s00044-011-9636-y]
[65]
Çapan İ.; Servi, S.; Dalkılıç, S.; Dalkılıç, L.K. Synthesis and anticancer evaluation of benzimidazole derivatives having norbornene/dibenzobarrelene skeletons and different functional groups. ChemistrySelect, 2020, 5(45), 14393-14398.
[http://dx.doi.org/10.1002/slct.202004034]
[66]
Mantu, D.; Antoci, V.; Moldoveanu, C.; Zbancioc, G. Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity. J. Enzyme Inhib. Med. Chem., 2016, 31, 96-103.
[67]
Błaszczak-Świątkiewicz, K.; Almeida, D.; Perry, M.; Mikiciuk-Olasik, E. Synthesis, anticancer activity and UPLC analysis of the stability of some new benzimidazole-4,7-dione derivatives. Molecules, 2013, 19(1), 400-413.
[http://dx.doi.org/10.3390/molecules19010400] [PMID: 24384922]
[68]
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]
[69]
Shinde, V.S.; Lawande, P.P.; Sontakke, V.A.; Khan, A. Synthesis of benzimidazole nucleosides and their anticancer activity. Carbohydr. Res., 2020, 498, 108178.
[http://dx.doi.org/10.1016/j.carres.2020.108178] [PMID: 33045644]
[70]
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]
[71]
Shaaban, M.A.E.; Kamal, A.M.; Teba, H.E.S. Synthesis, characterisation and biological screening of some 2-substituted benzimidazole derivatives as potential anticancer agents. J. Chem. Res., 2016, 40(4), 228-234.
[http://dx.doi.org/10.3184/174751916X14577069096465]
[72]
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]
[73]
Raka, S.C.; Rahman, A.; Hussain, F.; Rahman, S.M.A. Synthesis, characterization and in vitro, in vivo, in silico biological evaluations of substituted benzimidazole derivatives. Saudi J. Biol. Sci., 2022, 29(1), 239-250.
[http://dx.doi.org/10.1016/j.sjbs.2021.08.082] [PMID: 35002414]
[74]
Ren, B.; Liu, R.C.; Ji, K.; Tang, J.J.; Gao, J.M. Design, synthesis and in vitro antitumor evaluation of novel pyrazole-benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2021, 43, 128097.
[http://dx.doi.org/10.1016/j.bmcl.2021.128097] [PMID: 33979690]
[75]
Raducka, A.; Czylkowska, A.; Gobis, K.; Czarnecka, K. Szymański, P.; Świątkowski, M. Characterization of metal-bound benzimidazole derivatives, effects on tumor cells of lung cancer. Materials (Basel), 2021, 14(11), 2958.
[http://dx.doi.org/10.3390/ma14112958] [PMID: 34070886]
[76]
Kacar, S.; Unver, H.; Sahinturk, V. A mononuclear copper(II) complex containing benzimidazole and pyridyl ligands: Synthesis, characterization, and antiproliferative activity against human cancer cells. Arab. J. Chem., 2020, 13(2), 4310-4323.
[http://dx.doi.org/10.1016/j.arabjc.2019.08.002]
[77]
Goud, N.S.; Ghouse, S.M.; Vishnu, J.; Komal, D.; Talla, V.; Alvala, R.; Pranay, J.; Kumar, J.; Qureshi, I.A.; Alvala, M. Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents. Bioorg. Chem., 2019, 89, 103016.
[http://dx.doi.org/10.1016/j.bioorg.2019.103016] [PMID: 31185390]
[78]
Chen, X.; Yang, X.; Mao, F.; Wei, J.; Xu, Y.; Li, B.; Zhu, J.; Ni, S.; Jia, L.; Li, J. Development of novel benzimidazole-derived neddylation inhibitors for suppressing tumor growth in vitro and in vivo. Eur. J. Med. Chem., 2021, 210, 112964.
[http://dx.doi.org/10.1016/j.ejmech.2020.112964] [PMID: 33129593]
[79]
Tang, L.; Wu, W.; Zhang, C.; Shi, Z.; Chen, D.; Zhai, X.; Jiang, Y. Discovery of the PARP (poly ADP-ribose polymerase) inhibitor 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide for the treatment of cancer. Bioorg. Chem., 2021, 114, 105026.
[http://dx.doi.org/10.1016/j.bioorg.2021.105026] [PMID: 34186467]
[80]
Jian-Song. Gao, Q.L.; Wu, B.W.; Li, D.; Shi, L.; Zhu, T.; Lou, J.F.; Jin, C.Y.; Zhang, Y.B.; Zhang, S.Y.; Liu, H.M. Novel tertiary sulfonamide derivatives containing benzimidazole moiety as potent anti-gastric cancer agents: Design, synthesis and SAR studies. Eur. J. Med. Chem., 2019, 183, 111731.
[http://dx.doi.org/10.1016/j.ejmech.2019.111731] [PMID: 31577977]
[81]
Karadayi, F.Z.; Yaman, M.; Kisla, M.M.; Keskus, A.G.; Konu, O.; Ates-Alagoz, Z. Design, synthesis and anticancer/antiestrogenic activities of novel indole-benzimidazoles. Bioorg. Chem., 2020, 100, 103929.
[http://dx.doi.org/10.1016/j.bioorg.2020.103929] [PMID: 32464404]
[82]
Karthikeyan, C.; Solomon, V.R.; Lee, H.; Trivedi, P. Synthesis and biological evaluation of 2-(phenyl)-3H-benzo[d]imidazole-5-carboxylic acids and its methyl esters as potent anti-breast cancer agents. Arab. J. Chem., 2017, 10, S1788-S1794.
[http://dx.doi.org/10.1016/j.arabjc.2013.07.003]
[83]
Noolvi, M.; Agrawal, S.; Patel, H.; Badiger, A.; Gaba, M.; Zambre, A. Synthesis, antimicrobial and cytotoxic activity of novel azetidine-2-one derivatives of 1H-benzimidazole. Arab. J. Chem., 2014, 7(2), 219-226.
[http://dx.doi.org/10.1016/j.arabjc.2011.02.011]
[84]
Paul, K.; Bindal, S.; Luxami, V. Synthesis of new conjugated coumarin–benzimidazole hybrids and their anticancer activity. Bioorg. Med. Chem. Lett., 2013, 23(12), 3667-3672.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.071] [PMID: 23642480]
[85]
Rashid, M.; Husain, A.; Mishra, R. Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents. Eur. J. Med. Chem., 2012, 54, 855-866.
[http://dx.doi.org/10.1016/j.ejmech.2012.04.027] [PMID: 22608854]
[86]
Reddy, T.S.; Kulhari, H.; Reddy, V.G.; Bansal, V.; Kamal, A.; Shukla, R. Design, synthesis and biological evaluation of 1,3-diphenyl-1 H -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]
[87]
Camden, J.B. Methods of treating cancer with benzimidazoles. U.S. Patent 6,262,093, 2001.
[88]
Griffin, R.J.; Calvert, A.H.; Curtin, N.J.; Newell, D.R.; Golding, B.T. Benzimidazole compound. U.S. Patent 6,310,082, 2001.
[89]
Takayama, K.; Kimura, T.; Masuda, N.; Naito, R.; Okamoto, Y.; Koga, Y.; Okada, Y.; Takeuchi, M. Benzimidazole compound. International Patent 068,407, 2002.
[90]
Skalitzky, D.J.; Webber, S.E.; Eastman, B. Benzimidazole inhibitors of poly (ADP- ribosyl) polymerase. U.S. Patent 0,034,078, 2004.
[91]
Machajewski, T.D.; Hannah, A.; Harwood, E.; Haroldsen, E. Use of benzimidazolequinolinones for treating cancer. Canadian Patent 2,501,932, 2014.
[92]
Pfahl, M. Benzoxazole, benzothiazole, and benzimidazole derivatives for the treatment of cancer and other diseases. International Patent 066,952, 2004.
[93]
Beaulieu, F.; Marinier, A.; Ouellet, C.; Roy, S.; Wittman, M.D. Benzimidazole C-2 heterocycles as kinase inhibitors. U.S. Patent 0,054,655, 2005.
[94]
Breitenbucher, J.G.; Lee-dutra, A.; Neff, D.K. Aryl-substituted benzimidazole and imidazopyridine ethers as anti- cancer agents. Canadian Patent 2,572,218, 2013.
[95]
Bolger, J.; Castelhano, A.L.; Laufer, R.; Li, A.; Peter, C.; Smith, S.; Sun, Y. N-substituted pyrazolyl-amidyl-benzimidazolyl c-kit inhibitors. U.S. Patent 0,035,951, 2006.
[96]
Aso, K.; Mochizuki, M.; Kojima, T.; Kobayashi, K.; Pratt, S.A.; Gyorkos, A.C.; Corrette, C.P.; Cho, S.Y. Benzimidazole compounds. International Patent 051,533, 2008.
[97]
Lawrence, K. 2-((R)-methylpyrrolidin-2-yl)-1H-benzimidazole-4- carboxamide crystalline form 1. Australian Patent 310,781, 2009.
[98]
Kamal, A.; Praveen, K.P.; Seshadri, B.N.; Sreekanth, K. Novel benzimidazole linked pyrrolo[2,1-Q[1,4] benzodiazepine hybrids as potential antitumour agents and process for the preparation thereof. International Patent 113,085, 2009.
[99]
Goh, K.L.; Khng, H.H.; Sabanayagam, V.M.; Sangthongpitag, K.; Stunkel, W.; Tan, Y.C.; Wood, J.M. Combination of benzimidazole anti-cancer agent and a second anti-cancer agent. U.S. Patent 0,098,691, 2010.
[100]
Boezio, A.; Cheng, A.C.; Coats, J.R.; Copeland, K.W.; Graceffa, R.; Harmange, J.C.; Huang, H.; La, D.; Olivieri, P.R.; Peterson, E.A.; Schenkel, L. Indole/Benzimidazole compounds as Mtor Kinase inhibitors. International Patent 096,314, 2010.
[101]
Reweastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Giddens, A.C.; Tsang, K.Y. Pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy. U.S. Patent 249,099, 2010.
[102]
Rewcastle, G.W.; Tsang, K.Y.; Gamage, S.A.; Giddens, A.C. Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy. Canadian Patent 2,767,008, 2018.
[103]
Nair, S.K.; Planken, S.P. Benzimidazole derivatives. Canadian Patent 2,772,194, 2011.
[104]
Rewcastle, G.W.; Giddens, A.C.; Gamage, S.A. 1,3,5- triazinylbenzimidazole sulfonamides and their use in cancer therapy. International Patent 044,641, 2012.
[105]
Ahmed, K.; Pogula, P.K. Napthalimide-benzimidazole hybrids as potential antitumor agents and process for the preparation thereof. U.S. Patent 8,288,387, 2012.
[106]
Chang, C.S.; Guh, J.; Teng, C.; Pan, S.; Chang, W.; Liu, J.; Chang, K.; Kuo, S. Benzimidazole compounds and their use as anticancer agents. U.S. Patent 8,501,957, 2013.
[107]
Moussy, A.; Benjahad, A.; Schalon, C.; Pez, D.; Chevenier, E.; Sandrinelli, F.; Martin, J.; Picoul, W. Benzimidazole derivatives as selective protein kinase inhibitors. International Patent 202,763, 2014.
[108]
Rehwinkel, H.; Panknin, O.; Ring, S.; Anlauf, S.; Siebeneicher, H.; Nguyen, D.; Schwede, W.; Bauser, M.; Zimmermann, K.; Kaulfuss, S.; Neuhaus, R.; Blaney, P.M. Benzimidazol-2-amines as mIDH1 inhibitors. Australian Patent 217,788, 2015.
[109]
Qu, J.; Rivero, R.; Sanchez, R.; Tedesco, R. Benzimidazole derivatives as Pl3 kinase inhibitors. European Patent 2,624,696, 2016.
[110]
Owens, T.; Hill, R.J. Benzimidazole derivatives as RLK and ITK inhibitors. U.S. Patent 9,932,329, 2018.
[111]
Kim, J.; Song, K.; Kim, T. Novel benzimidazole derivatives, preparation method thereof and use thereof as anti-virus agent comprising the same. U.S. Patent 395,289, 2021.

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