Synthesis and Evaluation of Naphthalimides and their Hybrids with Other Heterocyclic Moieties for Anticancer and Antibacterial Activities

Abstract

People are mostly impacted by bacterial infections and cancer because of the emergence of drug resistance to currently marketed medications, even with the numerous approaches and treatments available. Despite years of intensive medicinal chemistry research and development, none of the medications were able to effectively treat bacterial infections or cancer because of their severe side effects, low margin safety, lack of specificity, and poor efficacy at target areas. New heterocyclic compounds with improved selectivity, no serious side effects, great efficiency, low toxicity to healthy cells, and more therapeutic effects than currently available medications are urgently needed to address this problem. In order to overcome these drawbacks and create novel therapeutic molecules with broad-spectrum action, numerous new compounds with good biological activity have been reported in the literature through modification, derivatization, and functionalization of naphthalimide, triazine, triazole, and coumarin. In this work, we have designed and synthesized naphthalimide and coumarin hybrids, naphthalimide and triazine hybrids, and bisnaphthalimides with and without the spacer. The synthesized molecules were characterized successfully by NMR and HRMS techniques. Following synthesis, these compounds were tested against a panel of 60 human cancer cell lines and Gram-positive and Gram-negative bacterial strains to determine their anticancer and antibacterial properties, respectively. To highlight the mechanism for anticancer activity, spectroscopic techniques were used to examine the binding interaction of the most effective drugs towards DNA and HSA. Membrane studies, biofilm inhibition, and other methods were used to investigate the antibacterial activity's mode of action. In conclusion, the synthesized compounds exhibited excellent anticancer and antibacterial properties with low cytotoxicity toward normal cell lines. Thus, our synthesized compounds have the potential to be taken further to clinical trials for their development as anticancer and antibacterial agents.