Recent Advances in the Development of Selected Triterpenoid-Based Hybrid Molecules and Their Antimicrobial Activities: A Review

Abstract

Triterpenoids are a diverse class of naturally occurring compounds with a wide range of pharmacological properties, including anticancer, anti-inflammatory, antimicrobial, and antiviral activities. Among them, ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA) have emerged as key scaffolds due to their broad therapeutic potential and structural versatility. However, the clinical application of these compounds is often limited by issues such as poor solubility, bioavailability, and selectivity. To address these challenges, research conducted between 2015 and 2025 increasingly focused on the development of triterpenoid-based hybrid molecules, in which the triterpenoid scaffolds are chemically linked to other bioactive pharmacophores. This approach aims to enhance therapeutic efficacy through synergistic action, improved pharmacokinetics, and multitarget interactions. This comprehensive review explores recent advancements in the design, synthesis, and evaluation of hybrid derivatives of selected triterpenoids, particularly UA, OA, and BA. Emphasis is placed on the structure-activity relationships (SARs), biological evaluations, and mechanisms of action of these hybrid compounds across various disease models. The review also highlights current challenges, research gaps, and future perspectives in the rational development of triterpenoid-based hybrids as potential leading candidates in drug discovery.