Endoperoxides: Highly Oxygenated Terpenoids with Anticancer and Antiprotozoal Activities

Endoperoxides represent a distinctive class of highly oxygenated terpenoids characterized by the presence of a cyclic peroxide (–O–O–) bond, a structural feature that underlies their remarkable chemical reactivity and broad spectrum of biological activities. Naturally occurring endoperoxides are widely distributed in terrestrial and marine organisms, including plants, algae, fungi, and bryophytes, and play important roles in chemical defense and ecological interactions. This review provides a comprehensive overview of naturally occurring endoperoxide-containing terpenoids, with particular emphasis on their distribution in nature, structural diversity, and biological activity profiles. Special attention is given to their antiprotozoal and anticancer properties, exemplified by artemisinin and related compounds, which remain among the most effective antimalarial agents and show promising antineoplastic potential. Using structure–activity relationship (SAR) concepts and modern computational approaches, including the PASS (Prediction of Activity Spectra for Substances) system, we analyze trends linking peroxide-containing motifs to biological function. Comparative evaluation of experimental and predicted activities highlights key structural features associated with antiprotozoal, antineoplastic, and anti-inflammatory effects. The review underscores the significance of endoperoxides as a rich source of bioactive scaffolds and discusses their potential for further development as therapeutic agents, despite challenges related to stability and reactivity.