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 β-lactam derivatives and a preliminary evaluation of their anticancer properties. The reactions were completely diastereoselective, leading exclusively to the formation ofcis- β-lactams11a –l andtrans-bis- β-lactams16a –g. All of these compounds were obtained in good to excellent yields and their structures were established based on IR,1H NMR,13C NMR spectral data, and elemental analysis. Each of the β-lactams was screened for antioxidant and anticancer activities. Our results showed that all the compounds lacked cytotoxicity againstHepG2 cells, whereas16a and16b exhibited excellent anticancer activity with IC50 values below 191.57  µM onMCF-7 cell line and also, bis- β-lactams16a –g showed excellent antitumor activity against theTC-1 cell line. Antioxidant experiments of16a –d by the diphenylpicrylhydrazyl (DPPH) assay showed IC50 values ranging from 7 to 32.3  µg/ml. Interaction of16a,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 (Kb) of the compounds varies as16a; 16b; 16e; 16g >  16d;16f. Interaction of16d with CT-DNA was also investigated by fluorescence spectroscopy. The results support an intercalative interaction of16d and16f and non-intercalation mechanism for16a,16b,16e, and16g.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research