engleski

Antiplasmodial activity of novel generation of triazole-type harmicines

According to the World Health Organization, malaria, a neglected tropical disease caused by the protozoal parasite Plasmodium, was responsible for more than 400 000 deaths in 2019 [1]. Due to the spread of a multidrug-resistant malaria parasite, the development of novel, more effective antimalarials is necessary. Previously, we covalently linked harmine and cinnamic acid derivatives (CADs), compounds with confirmed antimalarial activity, via triazole linker into hybrid molecules (harmicines) [2]. The promising antimalarial activity of the prepared hybrids encouraged us to design, synthesize and evaluate the biological activity of a new generation of harmicines differing in the position of substituents at the β-carboline core (Figure 1.). The antimalarial activity of the novel hybrids was evaluated in vitro against the erythrocytic stage of the Plasmodium life cycle. The hybrids based on 6-substituted β- carboline (1a-e) showed better antiplasmodial activity compared to harmine. Among them, m-Br- substituted derivative (1c) exerted the best antimalarial activity with IC50 value in the low submicromolar range. N9-substituted β- carboline alcohols (2a-e) have shown weaker activity compared to harmine. The exception is m- Br-substituted derivative (2c) which is slightly more active than harmine, but less than its analog at position 6 of the β-carboline core, leading to the conclusion that introduction of the hydroxy group at the position 3 of the β- carboline core resulted in decreased antiplasmodial activity.

malaria, hybrid compounds, harmine, cinnamic acid derivatives, "click" chemistry

nije evidentirano