The primary functions of cancer chemotherapeutic agents are not only to inhibit the growth or kill the cancer cells, but conventional cancer chemotherapy is highly inadequate as a result of the lack of selectivity between cancer and normal cells. This calls for novel cancer therapies for selectively targeting cancer cells without toxicity to normal cells. Extensive literature review revealed that compounds with substituted benzimidazole moiety showed potent anticancer activity. Amide linkage in the compound also gives additional important characteristic to compound for anticancer activity. Hence, 2-alkyl/aryl-N-substituted-1H-benzimidazole-5-carboxamide derivatives were designed based upon literature review and knowledge based structure activity relationship studies. All designed molecules were docked on human Topoisomerase-IIa ATPase-AMP-PNP complex [PDB: 1ZXM], a co-crystal structure taken from protein data bank (PDB) using Surflex. In all, 18 novel 2-alkyl/aryl-N-substituted-1H-benzimidazole-5-carboxamide derivatives, showing good docking score and important H-bonds with amino acids of protein, were synthesized. 2,4-diamino benzoic acid was reacted with various aliphatic and aromatic acids to yield 2-alkyl/aryl-1H-benzimidazole-5-carboxylic acid. This will further reacted with various aliphatic and aromatic amines in presence of DCC as acid-amine coupling agent to synthesize target compounds. All synthesized compounds were characterized by FT-IR, 1H NMR and Mass spectral analysis. Anti cancer activity of compounds was evaluated in-vitro on various cell lines viz. A-375 [Human Malignant Melanoma; Skin], DU-145 [Human Carcinoma; Prostate] and HCT-15 [Human Colorectal Adenocarcinoma; Colon] by XTT assay method using Doxorubicin as reference standard. Few of the synthesized compounds showed good anti proliferative activity against all cancer cell lines. Structure activity relationship (SAR) study compares effectiveness of synthesized compounds. The designed series of compounds can further exploit in search of novel anticancer agents.

Design, synthesis, and in-vitro biological activity of novel 2-alkyl/aryl-N-substituted-1H-benzimidazole-5-carboxamide derivatives as anticancer agents

245th National Meeting (2013)

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