DNA Damage and Intercalation by Elinafide Modified Bis-naphthalimides for their Anticancer Activity

Elinafide is a bis-intercalating naphthalimide, but due to serious side effects, it has failed in clinical trials phase II. In light of this, we have modified the elinifide and synthesized the new bis-naphthalimide by introducing an alkyl chain as a spacer between them. The derivatives are evaluated for their anticancer activity against 60 human cancer cell lines at 10 µM. The most active compounds, 5e and 9 h were further evaluated at five-dose concentrations (10−4–10−8 M). Low MG-MID GI50 values are observed for both the compounds 5e (33.32 µM) and 9h (4.67 µM). The mechanism is explored In vitro by performing ct-DNA binding studies through spectroscopic techniques such as UV–visible, fluorescence, and circular dichroism. From the results obtained, it is observed that compound 5e binds more strongly with DNA than 9h. Comet assay is also carried out to check the compound’s ability to damage DNA in the cancer cell. The binding ability of these compounds towards HSA is also examined, and the results suggested that compounds effectively bind to HSA and thus can be delivered to the target site easily. In addition, screening of 5a-i and 9a-i for their antibacterial properties against eight bacterial strains is performed. Results showed that 5h exhibited a broad spectrum of activity against all the tested bacterial strains, with MIC values ranging from 3.125 to 1.56 µg/ml.