Design, Synthesis, DNA Binding, Cytotoxicity, and Molecular Docking Studies of Amonafide-Linked beta-Lactam

摘要

abstract_textpThis study describes our investigations on the synthesis, molecular modeling, and biological capabilities of a new beta-lactam containing the anticancer agent, amonafide. This is the first time that amonafide has been applied to a beta-lactam synthesis, which involved five steps from naphthalic anhydride. The beta-lactam was structurally characterized by FT-IR, H-1 NMR, H C-13 NMR, mass spectra, and elemental analysis. UV-vis and fluorescence spectroscopy studies indicated that the beta-lactam is an effective DNA intercalating agent. Gel electrophoresis confirmed its intercalation into the pBluescript plasmic 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 beta-lactam was stacked tightly between DNA bases via the major groove. Moreover, the MTT assay of the beta-lactam against the HepG2 cancerous cell line showed potential cytotoxic behavior with an IC50 of 65.5 mu M and 34.2 mu 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 beta-lactam./p/abstract_text