Unlocking the cytotoxic potential of Apocynaceae monoterpene indole and <i>bis</i> -indole alkaloids: a review

Abstract

The Apocynaceae family is a key source of cytotoxic monoterpenoid indole and <i>bis</i>-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 <i>Tabernaemontana</i> and <i>Kopsia. Tabernaemontana</i> repeatedly yielded jerantinine derivatives, tabernaricatine A, conophyllidine, and substituted tabersonine, while <i>Kopsia</i> 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.