Naturally occurring triterpenoids from plants as potential agents against malaria: a review from 1994 to 2025.

Abstract

Malaria continues to pose a significant global health challenge, with the World Health Organization reporting an estimated 282 million cases and 610,000 deaths in 2024. The rapid spread of resistance to both chloroquine and artemisinin-based combination therapies by Plasmodium falciparum, confirmed in at least eight sub-Saharan African countries, highlights the urgent need for new antimalarial treatments. Triterpenoids derived from medicinal plants represent one of the most structurally diverse and pharmacologically promising classes of natural products for antimalarial drug discovery. These compounds are biosynthesized through the polymerization of six isoprene units, a process regulated by various enzymes. This document provides a comprehensive summary of data on antiplasmodial triterpenoids, compiled from primary literature spanning the last three decades, from 1994 to September 2025. It covers 279 structurally characterized compounds across 18 skeletal classes. The document includes an in-depth discussion on activity trends, structure-activity relationships (SAR), mechanistic findings, and multi-criteria evaluations for drug discovery. It also critically assesses key gaps and future research priorities. This work aims to offer valuable insights for researchers interested in exploring triterpenoid scaffolds for antimalarial drug development.