Antimalarial Potential of Synthetic Geraniol and Nerol Analogs

Abstract Drug resistance is a major threat to malaria control, and thus new drugs are required to fight against this parasitosis. To accelerate drug development, it is of special interest the exploration of natural compounds or repositioning drugs already employed for other diseases. Considering this, previous studies have found that diverse plant terpenes arrest Plasmodium parasites in vitro and in vivo models. However, most terpenes possess low toxicity for the parasite and/or face pharmacokinetic issues. Here, we report several new acyclic monoterpene analogs which possess great antiplasmodial activity in vitro (50% inhibitory concentration at low micromolar scale) against P. falciparum parasites. Also, in vitro studies using hepatocellular carcinoma cells (HepG2) demonstrated remarkable selectivity for malaria parasites. Furthermore, bioinformatic approaches revealed that these compounds possess acceptable pharmacological properties. All these results suggest that acyclic monoterpene analogues could serve as a promising starting point for the development of synthetic terpenes as antimalarial drugs.