CAMPTOTHECIN AND ITS ANALOGUES: A REVIEW ON THEIR CHEMOTHERAPEUTIC POTENTIAL

Camptothecin (CPT), a cytotoxic quinoline alkaloid originally isolated from Camptotheca acuminata, has gained significant attention for its potent anticancer properties. Its mechanism of action involves the inhibition of DNA topoisomerase I, an essential enzyme for DNA replication and transcription. Despite its promising activity, native camptothecin suffers from poor solubility, instability of its lactone ring at physiological pH, and severe side effects, which limit its clinical application. To overcome these limitations, extensive research has led to the development of various CPT analogues with improved pharmacokinetic profiles and reduced toxicity. Among these, topotecan and irinotecan have been successfully introduced into clinical practice, demonstrating efficacy against a broad spectrum of cancers, including ovarian, colorectal, and small-cell lung cancers. Other novel analogues, such as belotecan and exatecan, are currently under investigation, showing enhanced therapeutic indices and tumor selectivity. Structural modifications of the A and B rings, and substitutions at position 7 and 10 of the CPT molecule, have been particularly effective in enhancing activity and overcoming resistance mechanisms. This review summarizes the current understanding of camptothecin and its analogues, focusing on their mechanisms of action, structure-activity relationships, pharmacological advancements, and clinical relevance. The continual evolution of CPT derivatives underscores their enduring role as valuable chemotherapeutic agents and highlights the importance of rational drug design in optimizing anticancer therapy.

Keywords: Camptothecin, Topoisomerase I inhibitors, Chemotherapy, CPT analogues, Anticancer agents, Drug design.