Design, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic molecules on (HCT-116) colon cancer cells

A novel series of benzimidazole derivatives with methoxylated aryl groups was designed and synthesized as molecules with potential cytotoxic activity. In vitro cytotoxic activity over HCT-116 cells showed that N-(benzimidazothiazolone)acetamides 11a, 11b and 11c were found to be the most cytotoxic compounds compared camptothecin (CPT). The tested compounds had a dual topoisomerase I-β (Topo I-β) and tubulin inhibiting activities when compared to CPT and Podophyllotoxin (Podo) where, compounds l0a, l0b, 11a and 11b exhibited a potent inhibitory activity on Topo I-β enzyme in nano-molar concentration, on the other hand, compounds 12b and 13b exhibited the best inhibitory activity β-tubulin polymerization. Results of the cell cycle analysis as well as the results of annexin-V on HCT-116 cells showed that benzimidazothiazoles 12b and 13b had a pro-apoptotic activity higher than CPT by 1.33- and 1.30-folds, respectively. Moreover, the concentration of p53, Bax/Bcl-2 ratio and caspase 3/7 increased in compounds l0b, 11b, l2b, 13b, especially, compounds 11b and 13b exhibited an increased level of these mediators than CPT. Finally, compound 11b regulated the radiosensitizing activity of the HCT-116 cells by modulating the chromosomal instability. [Display omitted] •The synthetic molecules were designed as dual antitumor and radiosensitizer agents.•Compound 11b exhibited potent cytotoxic activity on HCT-116 cancer cells higher than camptothecin (CPT).•in vitro topoisomerase assay correlated cytotoxicity of molecule 11b to DNA synthesis inhibition.•Compound 11b could regulate the radio-sensitizing activity of the (HCT-116) cells by modulating the Chromosomal Instability of Multipolar Mitosis (MM), Mitotic Catastrophe (MC), Binucleated Cells (BN), Micronuclei (MN), Nuclear Bleb (NB), and Apoptotic Cells (AC).