Harmine derivatives as potential antimalarials

Malaria is a deadly mosquito-borne tropical and subtropical disease, caused the parazite of the genus Plasmodium. There is neither available vaccine, nor reliable vector control. In addition, Plasmodium is developing resistance to the existing therapy, which urges the discovery of novel drugs with new mechanisms of action. Alkaloids of b-carboline type are present in the medicinal plants Peganum harmala and Eurycoma longifolia, which have been used in the traditional Oriental medicine for the treatment of cancer and malaria. The active ingredients were identified as harmine, harmaline, harmalol and harman. In vitro and in vivo studies have proven harmine’s antimalarial activity. Its possible mechanism of action is selective inhibition of P. falciparum heat shock protein 90, which is crucial for the parazite development and may play a major role in drug resistance. The final compounds will incorporate 1H-1,2,3-triazole scaffolds, which proved to be useful in the synthesis of various biologically active compounds. Standard methods of synthetic organic chemistry, as well as modern approaches, such as click chemistry and microwave assisted synthesis will be employed. Antimalarial activity of the prepared compounds will be evaluated in vitro on both erythrocytic and hepatic stage of the Plasmodium, as well as cytotoxycity against human cell lines. In addition, metabolism studies for the biologically active compounds will be performed. As a final result, this project will provide new candidate therapeutics against drug-resistant malaria parasite. The most active compounds will offer a valuable starting point for future development of innovative medicines.

Drug-based Strategies

Dec 2021 — Dec 2025

Croatia