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Synthesis, Heterocyclization and Anti-Tumour Activity Evaluation of Some Benzimidazole Derivatives


Affiliations
1 Faculty of Science, Department of Chemistry, Zagazig University, Egypt
 

Methylbenzimidazole 1 is converted to imidazole acrylic acid 3 via cyclo condensation with chloral followed by hydrolysis. Compound 3 also obtained from the reaction of o-phenylenediamine with maleic anhydride. Treatment of 1 with SeO2 yielded the oxidized product 4 (Aldehyde 4) which undergoes Wittig reaction using ester and Ph3P to furnish the acrylates 5. Compound 5 is also obtained by cyclocondensation of o-phenylenediamine and the corresponding maleate. Cyclization of 3 using Ac2O provides pyrroloimidazole 6. Imidazole 6 undergoes several transformations using HCl, ammonium hydroxide in neutral medium, o-phenylene diamine/HCl to provide acrylic acid 3, amide 7 and/or bicompound 8 respectively. Anilide 9 is obtained as a result of condensation of 3 with amines. Ester 5 undergoes 1,4-addition to benzimidazole ring to give the corresponding anilino derivative 10. Pyridazine cyclization is acheived by treatment of 5 with NH2OH in acidic medium. In vitro cytotoxicity is evaluated using SRB (sulphorhodamine-B) assay against two human cell lines, breast and liver carcinoma cell lines. The results show that compound 11 has strong activity against all cell lines tested.

Keywords

Active Methylene, Benzimidazoles, Cytotoxicity Activity, Hydrazines, Lactambenzimidazole.
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  • Gharib, A., Khorasani, H., Jahangir, B. R., Roshani, M., Bakhtiari, L. and Mohadeszadeh, S., Synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted-1H-imidazole derivatives and or 2,4,5triaryloxazoles using of silica-supported Preyssler nanoparticles. Bulg. Chem. Commun., 2014, 46, 165–174.

  • Trujillo, I. et al., 2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor. Bioorg. Med. Chem. Lett., 2009, 19, 908–911.

  • Palkowitz, A. D. et al., Structural evolution and pharmacology of a novel series of Triacid Angiotensin II Receptor Antagonists. J. Med Chem., 1994, 37, 4508–4521.

  • Chang, L. L. et al., Substituted imidazoles as glucagon receptor antagonist. Bioorg. Med Chem Lett., 2001, 11, 2549–2553.

  • Sharma, D., Narasimhan, B., Kumar, P., Judge, V., Narang, R., De Clercq, E. and Balzarini, J., Synthesis, antimicrobial and antiviral evaluation of substituted imidazole derivatives. Eur. J. Med. Chem., 2009, 44, 2347–2353.

  • Laufer, S. and Koch, P., Towards the improvement of the synthesis of novel 4(5)-aryl-5(4)-heteroaryl-2-thio-substituted imidazoles and their p38 MAP kinase inhibitory activity. Org. Biomol. Chem., 2008, 6, 437–439.

  • Kumar, S., Boehm, J. and Lee, J. C., MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat. Rev. Drug Discov., 2003, 2, 717–226.

  • King, A. J. et al., Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res., 2006, 66, 11100–11105.

  • Lambardino, J. G. and Wiseman, E. H., Preparation and antiinflammatory activity of some nonacidic trisubstituted imidazoles. J. Med. Chem., 1974, 17, 1182–1188.

  • Takle, A. K. et al., The identification of potent and selective imidazolebased inhibitors of B-Raf kinase. Bioorg. Med. Chem. Lett., 2006, 16, 378–381.

  • Kumar, Y. C. S., Malviya, M., Sharath Chandra, J. N. N., Kavitha, C. V., Thimmegowda, N. R., Subhash, M. N. and Rangappa, K. S., Effect of novel N-aryl urea substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s dementia models. Arkivoc, 2009, IX, 45–56.

  • Mohammed, M., Arul. K., Anjana, K. and Remya, K., Synthesis, docking studies and pharmacological evaluation of imidazole analogues of arecoline. Int. J. Curr. Pharm. Res., 2014, 6, 22–26.

  • Safari, J., Gandomi-Ravandi, S. and Naseh, S., Efficient, green and solvent-free synthesis of tetrasubstituted imidazoles using SbCl3/SiO2 as heterogeneous catalyst. J. Chem. Sci., 2013, 125, 827–833.

  • Banfi, E. et al., Antifungal and antimycobacterial activity of new imidazole and triazole derivatives. A combined experimental and computational approach. J. Antimicrob. Chemother., 2006, 58, 76–84.

  • Mamolo, M. G. et al., Antifungal and antimycobacterial activity of new N-1-[1-aryl-2-(1H-imidazol-1-yl and 1H-1,2,4-triazol-1-yl)ethylidene]-pyridine-2-carboxamidrazone derivatives: a combined experimental and computational approach. Arkivoc, 2004, V, 231–250.

  • Ahmad, Z., Sharma, S. and Khuller, G. K., In vitro and ex vivo antimycobacterial potential of azole drugs against Mycobacterium tuberculosis H37Rv. FEMS Microbiol. Lett., 2005, 251, 19–22.

  • Zampieri, D., Mamo, M. G., Laurini, E., Scialino, G., Banfi, E. and Vio, L., 2-aryl-3-(1H-azol-1-yl)-1H-indole derivatives: a new class of antimycobacterial compounds – conventional heating in comparison with MW-assisted synthesis. Arch. Pharm., 2009, 342, 716–722.

  • Chauhan, P. M. S., Sunduru, N. and Sharma, M., Recent advances in the design and synthesis of heterocycles as anti-tubercular agents. Future Med. Chem., 2010, 2, 1469–1500.

  • Skehan, P., Storeng, R., Scudiero, D., Monks, A. and McMahon, J., New colorimetric cytotoxicity assay for anticancer drug screening. J. Natl. Cancer Inst., 1990, 82, 1107–1112.


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  • Synthesis, Heterocyclization and Anti-Tumour Activity Evaluation of Some Benzimidazole Derivatives

Abstract Views: 291  |  PDF Views: 112

Authors

M. F. El-Ahwany
Faculty of Science, Department of Chemistry, Zagazig University, Egypt
Mohamed H. M. Abd El-Azim
Faculty of Science, Department of Chemistry, Zagazig University, Egypt

Abstract


Methylbenzimidazole 1 is converted to imidazole acrylic acid 3 via cyclo condensation with chloral followed by hydrolysis. Compound 3 also obtained from the reaction of o-phenylenediamine with maleic anhydride. Treatment of 1 with SeO2 yielded the oxidized product 4 (Aldehyde 4) which undergoes Wittig reaction using ester and Ph3P to furnish the acrylates 5. Compound 5 is also obtained by cyclocondensation of o-phenylenediamine and the corresponding maleate. Cyclization of 3 using Ac2O provides pyrroloimidazole 6. Imidazole 6 undergoes several transformations using HCl, ammonium hydroxide in neutral medium, o-phenylene diamine/HCl to provide acrylic acid 3, amide 7 and/or bicompound 8 respectively. Anilide 9 is obtained as a result of condensation of 3 with amines. Ester 5 undergoes 1,4-addition to benzimidazole ring to give the corresponding anilino derivative 10. Pyridazine cyclization is acheived by treatment of 5 with NH2OH in acidic medium. In vitro cytotoxicity is evaluated using SRB (sulphorhodamine-B) assay against two human cell lines, breast and liver carcinoma cell lines. The results show that compound 11 has strong activity against all cell lines tested.

Keywords


Active Methylene, Benzimidazoles, Cytotoxicity Activity, Hydrazines, Lactambenzimidazole.

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DOI: https://doi.org/10.18520/cs%2Fv115%2Fi2%2F310-314