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

Abstract

AbstractThis 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, 1H NMR, 13C 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 IC50 of 65.5 μM and 34.2 μM 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.