Unlocking the cytotoxic potential of Apocynaceae monoterpene indole and bis-indole alkaloids: a review.

The Apocynaceae family is a key source of cytotoxic monoterpenoid indole and bis-indole alkaloids with anticancer potential. This review examined 163 alkaloids reported across all family genera from 2000 to 2025; about 65% showed potent activity (IC50 ≤ 10 μM) against breast, lung, colon, skin, prostate, blood, and liver cancer cell lines using mainly MTT and SRB assays, with several demonstrating sub-micromolar potency. The most active compounds largely originated from Tabernaemontana and Kopsia. Tabernaemontana repeatedly yielded jerantinine derivatives, tabernaricatine A, conophyllidine, and substituted tabersonine, while Kopsia provided valparicine, kopsiarborine B, kopsiafrutine E, and kopsifine, all showing broad low- to sub-micromolar cytotoxicity. Structure-activity analyses link bis-indole frameworks and defined substitutions with enhanced potency. Although mechanistic evidence remains limited, reported pathways commonly involve apoptosis induction and cell-cycle arrest. Such findings reveal promising Apocynacae genera and structure-guided opportunities for anticancer drug development while underscoring the need for toxicity evaluation, pharmacokinetic profiling, and scalable production strategies.