Design and synthesis of a cannabidiol-oleoside hybrid molecules targeting lipoxygenases for inflammation management

The chemical coupling of natural bioactive compounds is currently a promising strategy for the design of novel therapeutic agents with enhanced activity. In this study, we designed and synthesized a hybrid compound combining cannabidiol (CBD), a characteristic molecule of Cannabis sativa and oleoside, from Olea europaea . The focus was to improve the already existing anti-inflammatory efficacy of the two “building blocks” through targeted inhibition of lipoxygenases (LOXs). CBD, a non-psychoactive cannabinoid, is known to inhibit 5-lipoxygenase (5-LOX), the key enzyme in the biosynthesis of pro-inflammatory leukotrienes [ 1 ]. Oleoside and its derivative oleacein exhibit anti-inflammatory properties seemingly via cyclooxygenase (COX) inhibition, with indications of additional effects on LOX pathways [ 2 ]. First data suggest that the newly developed CBD-oleoside hybrids ([ Fig. 1 ]) results in significant 5-LOX inhibition. Specifically, they show a more potent anti-inflammatory profile, making it a promising candidate for treating 5-LOX-driven diseases, such as asthma, arthritis, Alzheimer and cardiovascular disorders. Fig. 1 Basic skeleton of hybrid molecule CBD-Oleoside. Acknowledgement: This project is carried out within the framework of the National Recovery and Resilience Plan Greece 2.0, TAEDR-0534767, funded by the European Union – NextGenerationEU. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany