Synthesis, characterization and in vivo biological evaluation of novel benzimidazoles as potential anticancer agents

Authors

  • Rangaswamy Roopashree
  • Chakrabhavi Dhananjaya Mohan
  • Toreshettahally Ramesh Swaroop
  • Swamy Jagadish
  • KANCHUGARAKOPPAL SUBBEGOWDA RANGAPPA Department of Studies in Chemistry, University of Mysore, Mysore

Abstract

Objective: Cancer is one of the major cause of death worldwide irrespective of the sex. The aim of the study is to design, synthesize and identification of novel anti-proliferative agents that can potently target cancer.

Methodology: We are reporting the synthesis of new series of N-substituted 2-(2-butyl-4-chloro-1H-imidazole-5-yl)-1H-benzo[d]imidazole derivatives and evaluated for their anti-tumor activity against HeLa cell lines. We identified the lead compound in the series and tested its anti-proliferative and anti-angiogenic properties against EAT bearing mice.

Results: We identified 2-(2-butyl-4-chloro-1-heptyl-1H-imidazol-5yl)-1H-benzo[d]imidazole as a lead compound with the IC50 of 25.3 µM. The lead compound is significantly decreases angiogenesis in peritoneum of EAT bearing mice.

Conclusion: Our results clearly demonstrates that benzimidazoles suppresses the cell proliferation, peritoneal angiogenesis and ascites volume.

References

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.

Sumalatha D, Nithya TG. In vitro anti-oxidant and anticancer activity of Murraya koenigii against human colon cancer HT-29 cell lines. Asian J Pharm Clin Res 2014;7:83-6.

Gurupadaswamy HD, Girish V, Kavitha CV, Raghavan SC, Khanum SA. Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents. Eur J Med Chem 2013;63:536-43.

Marusyk A, Polyak K. Tumor heterogeneity: Causes and consequences. Biochim Biophys Acta 2010;1805(1):105-17.

Kreeger PK, Lauffenburger DA. Cancer systems biology: A network modeling perspective. Carcinogenesis 2010;31(1):2-8.

Koronkiewicz M, Romiszewska A, Kazimierczuk Z, Chilmonczyk Z. Anticancer activity of benzimidazole derived isothioureas in vitro. Ann Oncol 2013;24:i23.

Oksuzoglu E, Tekiner-Gulbas B, Alper S, Temiz-Arpaci O, Ertan T, Yildiz I, et al. Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors. J Enzyme Inhib Med Chem 2008;23(1):37-42.

Ries UJ, Mihm G, Narr B, Hasselbach KM, Wittneben H, Entzeroth M, et al. 6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: Synthesis, biological activity, and structure-activity relationships. J Med Chem 1993;36:4040-51.

Yurttas L, Demirayak S, Çiftçi GA, Yildirim SU, Kaplancikli ZA. Synthesis and biological evaluation of some 1,2-disubstituted benzimidazole derivatives as new potential anticancer agents. Arch Pharm (Weinheim) 2013;346:403-14.

Iwahi T, Satoh H, Nakao M, Iwasaki T, Yamazaki T, Kubo K, et al. Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against Helicobacter pylori. Antimicrob Agents Chemother 1991;35(3):490-6.

Townsend LB, Devivar RV, Turk SR, Nassiri MR, Drach JC. Design, synthesis, and antiviral activity of certain 2,5,6-trihalo-1-(beta-D-ribofuranosyl) benzimidazoles. J Med Chem 1995;38(20):4098-105.

Sondhi SM, Singh N, Kumar A, Lozach O, Meijer L. Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3)inhibition activity evaluation of benzimidazole/benzoxazole derivatives and some Schiff’s bases. Bioorg Med Chem 2006;14(11):3758-65.

Göker H, Ertan R, Akgün H, Yulug N. Synthesis and antifungal activity of some new benzimidazole derivatives. Arch Pharm (Weinheim)1991;324:283-6.

Vinodkumar R, Vaidya SD, Siva Kumar BV, Bhise UN, Bhirud SB, Mashelkar UC. Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(4-phenylethynyl-phenyl)-1H-benzimidazoles and N-substituted 2[4-(4,4-dimethyl-thiochroman-6-yl-ethynyl)-phenyl)-1H-benzimidazoles. Eur J Med Chem 2008;43:986-95.

Kus C, Ayhan-Kilcigil G, Can Eke B, Iscan M. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch Pharm Res 2004;27(2):156-63.

Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost 2007;98(1):155-62.

Kalliomäki J, Annas P, Huizar K, Clarke C, Zettergren A, Karlsten R, et al. Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in human capsaicin-induced pain and hyperalgesia. Clin Exp Pharmacol Physiol 2013;40(3):212-8.

Nakano H, Inoue T, Kawasaki N, Miyataka H, Matsumoto H, Taguchi T, et al. Synthesis of benzimidazole derivatives as antiallergic agents with 5-lipoxygenase inhibiting action. Chem Pharm Bull 1999;47:1573-78.

Abonia R, Cortés E, Insuasty B, Quiroga J, Nogueras M, Cobo J. Synthesis of novel 1,2,5-trisubstituted benzimidazoles as potential antitumor agents. Eur J Med Chem 2011;46(9):4062-70.

Ranganatha SR, Kavitha CV, Vinaya K, Prasanna DS, Chandrappa S, Raghavan SC, et al. Synthesis and cytotoxic evaluation of novel 2-(4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1H-benzo[d]imidazole derivatives. Arch Pharm Res 2009;32(10):1335-43.

Kumar CA, Jayarama S, Basappa, Salimath BP, Rangappa KS. Pro-apoptotic activity of imidazole derivatives mediated by up-regulation of Bax and activation of CAD in Ehrlich Ascites Tumor cells. Invest New Drugs 2007;25(4):343-50.

Chandru H, Sharada AC, Bettadaiah BK, Kumar CS, Rangappa KS, Sunila, et al. In vivo growth inhibitory and anti-angiogenic effects of synthetic novel dienone cyclopropoxy curcumin analogs on mouse Ehrlich ascites tumor. Bioorg Med Chem 2007;15(24):7696-703.

Keerthy HK, Mohan CD, Siveen KS, Fuchs JE, Rangappa S, Sundaram MS, et al. Novel synthetic biscoumarins target tumor necrosis factor-a in hepatocellular carcinoma in vitro and in vivo. J Biol Chem 2014.

Bellamakondi PK, Godhavarthi A, Ibrahim M, Kulkarni S, Naik RM, Maradam S. In vitro cytotoxicity of Caralluma species by MTT and trypan dye exclusion. Asian J Pharm Clin Res 2014;7:17-9.

Prabhakar BT, Khanum SA, Jayashree K, Salimath BP, Shashikanth S. Anti-tumor and proapoptotic effect of novel synthetic benzophenone analogues in Ehrlich ascites tumor cells. Bioorg Med Chem 2006;14(2):435-46.

Gaonkar SL, Lokanatha Rai KM, Suchetha Shetty N. Microwave-assisted synthesis and evaluation of anti-inflammatory activity of new series of N-substituted 2-butyl-5-chloro-3 H-imidazole-4-carbaldehyde derivatives. Med Chem Res 2009;18:221-30.

Vijay Avin BR, Thirusangu P, Lakshmi Ranganatha V, Firdouse A, Prabhakar BT, Khanum SA. Synthesis and tumor inhibitory activity of novel coumarin analogs targeting angiogenesis and apoptosis. Eur J Med Chem 2014;75:211-21.

Published

2014-11-01

How to Cite

Roopashree, R., C. D. Mohan, T. R. Swaroop, S. Jagadish, and K. S. . RANGAPPA. “Synthesis, Characterization and in Vivo Biological Evaluation of Novel Benzimidazoles As Potential Anticancer Agents”. Asian Journal of Pharmaceutical and Clinical Research, vol. 7, no. 5, Nov. 2014, pp. 309-13, https://innovareacademics.in/journals/index.php/ajpcr/article/view/1875.

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