Cytotoxicity, anticancer, and antioxidant properties of mono and bis-naphthalimido β-lactam conjugates

This article reports the diastereoselective synthesis of some novel naphthalimido and bis-naphthalimido beta-lactam derivatives and a preliminary evaluation of their anticancer properties. The reactions were completely diastereoselective, leading exclusively to the formation of cis-beta-lactams 11a-l and trans-bis-beta-lactams 16a-g. All of these compounds were obtained in good to excellent yields and their structures were established based on IR, H-1 NMR, C-13 NMR spectral data, and elemental analysis. Each of the beta-lactams was screened for antioxidant and anticancer activities. Our results showed that all the compounds lacked cytotoxicity against HepG2 cells, whereas 16a and 16b exhibited excellent anticancer activity with IC50 values below 191.57 mu M on MCF-7 cell line and also, bis-beta-lactams 16a-g showed excellent antitumor activity against the TC-1 cell line. Antioxidant experiments of 16a-d by the diphenylpicrylhydrazyl (DPPH) assay showed IC50 values ranging from 7 to 32.3 mu g/ml. Interaction of 16a, 16b, 16d-g with calf-thymus DNA (CT-DNA) was also supported by absorption titration studies. The compounds exhibit good binding propensity to CT-DNA and the DNA binding affinity (K-b) of the compounds varies as 16a; 16b; 16e; 16g > 16d; 16f. Interaction of 16d with CT-DNA was also investigated by fluorescence spectroscopy. The results support an intercalative interaction of 16d and 16f and non-intercalation mechanism for 16a, 16b, 16e, and 16g.