engleski

Antiplasmodial activity of novel amide-type harmicines

Malaria is one of the most prevalent human infectious diseases caused by the parasites of the genus Plasmodium (1). Spread of the multidrug resistant Plasmodium strains, particularly P. falciparum in Southeast Asia, urges the discovery of agents with novel mechanisms of action (2). Previously, we synthesized amide-type harmicines, i.e. hybrid compounds consisting of β-carboline alkaloid harmine and cinnamic acid derivatives, which exerted significant antiplasmodial activity (3). Therefore, we prepared novel amide-type harmicines at the positions C-1, C-3 and O-6 of harmine’s β-carboline core, 1a-h, 2a-h and 3a-h, respectively (Figure). Here we disclose the results of the in vitro screening of their blood schizonticidal activities against two strains of P. falciparum (chloroquine-sensitive, Pf3D7 and chloroquine-resistant strain, PfDd2). The analysis of the obtained results has shown that the antiplasmodial activities decreased according to the pattern: 3 ˃ 2 > 1. Harmicines 2 and 3 displayed antiplasmodial activities in low micromolar and submicromolar concentrations, whereas harmicines 1 were inactive at the highest concentration tested. Notably, compound 3d, m- trifluoromethylcinnamic acid derivative, exhibited the highest antiplasmodial activities with IC50 values 0.12 ± 0.02 µM and 0.32 ± 0.08 µM for Pf3D7 and PfDd2 strains, respectively.

Malaria ; Plasmodium ; β-carboline ; amide-type harmicines

nije evidentirano