Bhat Aeyaz Ahmad, Gacem Amel, Qasim Maytham T, Almulla Nuha, Muzammil Khursheed, Shalabi Manar G
Department of Chemistry, Lovely Professional University, Phagwara, Punjab, 144411, India.
Department of Physics, Faculty of Sciences, University 20 Août 1955, Skikda, Algeria.
Mol Divers. 2025 Jun 18. doi: 10.1007/s11030-025-11251-1.
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.
1,8-萘二甲酰亚胺衍生物因其高效的DNA嵌入能力和多样的作用机制，包括对拓扑异构酶I/II的抑制以及光诱导的DNA裂解，已成为抗癌药物开发中通用的骨架结构。这些结构特征赋予了它们强大的细胞毒性和广谱抗癌活性。本手稿重点且全面地概述了基于1,8-萘二甲酰亚胺的嵌入剂在设计和生物学评价方面的最新进展。这些化合物被系统地分类为单嵌入剂、稠环扩展类似物、光活性剂、双功能缀合物和有机金属杂化物。对于每一类，我们讨论了与抗癌疗效相关的构效关系、细胞毒性概况和作用机制见解。与以往的综述不同，这项工作提供了跨多个结构类别的综合观点，强调了它们的转化潜力，并为基于萘二甲酰亚胺的治疗药物的未来合理设计提供指导。
