Design, Synthesis, DNA Binding, Cytotoxicity, and Molecular Docking Studies of Amonafide‐Linked β ‐Lactam

This study describes our investigations on the synthesis, molecular modeling, and biological capabilities of a new β ‐lactam containing the anticancer agent, amonafide. This is the first time that amonafide has been applied to a β ‐lactam synthesis, which involved five steps from naphthalic anhydride. The β ‐lactam was structurally characterized by FT‐IR, 1 H NMR, 13 C NMR, mass spectra, and elemental analysis. UV‐vis and fluorescence spectroscopy studies indicated that the β ‐lactam is an effective DNA intercalating agent. Gel electrophoresis confirmed its intercalation into the pBluescript plasmid DNA, causing a considerable decrease in its electrophoretic mobility. The gel electrophoresis pattern in the presence of ethidium bromide, acridine orange, and methyl green also demonstrated that the β ‐lactam was stacked tightly between DNA bases via the major groove. Moreover, the MTT assay of the β ‐lactam against the HepG2 cancerous cell line showed potential cytotoxic behavior with an IC 50 of 65.5  μ M and 34.2  μ M after 48 and 72 h incubation, respectively. Molecular docking experiments were also in agreement with the experimental data and showed the major groove binding behavior of the β ‐lactam.