1,8-naphthalimide-based DNA intercalators and anticancer agents: a systematic review

Abstract

1,8-Naphthalimide derivatives have emerged as versatile scaffolds in anticancer drug development due to their efficient DNA-intercalating ability and diverse mechanisms of action, including Topoisomerase I/II inhibition and photoinduced DNA cleavage. These structural features contribute to their potent cytotoxicity and broad-spectrum anticancer activity. This manuscript offers a focused yet comprehensive overview of recent advances in the design and biological evaluation of 1,8-naphthalimide-based intercalators. The compounds are systematically categorized into mono-intercalators, fused-ring-extended analogs, photoactive agents, bifunctional conjugates, and organometallic hybrids. For each class, we discuss structure-activity relationships, cytotoxic profiles, and mechanistic insights relevant to anticancer efficacy. Distinct from previous reviews, this work provides an integrated perspective across multiple structural classes, emphasizing their translational potential and guiding future rational design of naphthalimide-based therapeutics.

Keywords: 1,8-Naphthalimide; Anticancer agents; DNA intercalation; Fused-ring derivatives; Mono-intercalators; Structure–activity relationship (SAR).