Potential Anticancer Agents: Design, Synthesis of New Pyrido[1,2-a]benzimidazoles and Related Derivatives Linked to Alkylating Fragments

The incentive of the present work has been primarily directed towards the design and synthesis of some novel pyrido[1,2-a]benzimidazoles with specific functionalities believed to have alkylation ability. This combination of pharmacological agents may enable synergistic anticancer effect. Nine compounds 5b, 13a, 13d, 13e, 14b, 14c, 15, 16, and 17 were selected by the National Cancer Institute (NCI), Bethseda, Maryland, USA to be evaluated for their in vitro antitumor activity. All the selected compounds were tested initially at a single dose (10 μM) in the full NCI 60 cell panel including leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast cancer cell lines. Majority of the test compounds exhibited moderate cytotoxic activity. The highest activity in all the investigated cancer cells was displayed by 14c against melanoma SK-MEL-5 cell line. This may be due to the impact of the lipophilic trifluoromethyl substitution on the biological activity profile.