Anticancer Evaluation of Some New 4β‐Imidazolopodophyllotoxin ‐Aromatic Amides

Herein, we described the synthesis of some new aromatic amides of 4β‐imidazolopodophyllotoxin (6 a–p) and their anticancer evaluation against four human cancer cell lines like MCF‐7 (breast), A549 (lung), Hela (cervical) and DU‐145 (prostate). Out of all, compounds 6 d, 6 e, 6 g, 6 i, 6 j, 6 l, 6 n and 6 o were found to be active with IC50 values in the range of 0.59‐10 μM. Specifically, compound 6 o showed greater potency against all the cell lines than the standard etoposide. Predominantly, compounds 6 e, 6 j and 6 o observed to be 3 to 4 times more potent against DU‐145 than the standard. The molecular docking studies of three active compounds 6 e, 6 j and 6 o on target protein DNA topoisomerase II were also conducted and found that binding affinity and free energies obtained were in good covenant with the corresponding IC50 values. Finally, the results of in silico ADMET revealed that, compounds 6 e, 6 j and 6 o have shown 100 % intestinal absorption and none of them exhibited AMES and hepato toxicity. The design and synthesis of some new aromatic amides of 4β‐imidazolopodophyllotoxin (6 a–p) was described herein. Among them, eight compounds namely 6 d, 6 e, 6 g, 6 i, 6 j, 6 l, 6 n and 6 o were observed to be active on MCF‐7, A549, Hela and DU‐145 cell lines. In specific, compound 6 o had superior potency against all the cell lines than the etoposide. Predominantly, compounds 6 e, 6 j and 6 o were observed to be 3 to 4 times more potent against DU‐145 than the etoposide. The results of in silico studies of three active compounds 6 e, 6 j and 6 o were also supported the corresponding anticancer activity data.