Molecular modelling assisted design of napthalimide-dihydropyrimidinone conjugates as potential cytotoxic agents

A molecular modelling assisted design of napthalimide-dihydropyrimidinone conjugates as potential cytotoxic agents based on a lead molecule (elinafide) is described. One of the napthalimide moiety and the amino groups in the lead molecule are replaced with dihydropymidinone and methylene motifs, respectively. The resulting chemical templates were subjected to molecular docking analysis at specific DNA intercalation site. Promising docking scores were obtained, which were better than the lead molecule suggesting the DNA intercalating ability of these conjugates. The conjugates were synthesized by a short and convenient synthetic route and this was followed by evaluation of cytotoxic properties against selected cancer cell lines. Conjugate 5f was the most active from the series that showed activity comparable to the standard against HCT-15 cell line. The molecular descriptor & drug likeliness of these conjugates were predicted computationally, and the undertaken study provided useful insights for further development of these interesting conjugates.