engleski

Antiplasmodial activity of triazole-type harmiquins

Global malaria control is being disrupted by the emergence of drug resistance to most of the available antimalarials, necessitating the search for novel drugs.[1] A recent rational approach used in the antimalarial drug design involves linking two bioactive molecules into a single chemical entity, i. e. preparing hybrid compounds.[2] Herein, we represent harmiquins, hybrids constituted of two moieties with pronounced antimalarial properties, -carboline alkaloid harmine and 7-chloroquinoline, [2, 3] linked via 1H-1, 2, 3-triazole (Figure). Antimalarial activity of novel hybrids was evaluated in vitro against the erythrocytic stage of the Plasmodium life cycle, revealing compound 8 as the most active (IC50 value 11.6±3.8 nM). Furthermore, the diversity of harmiquins allowed us to draw several conclusions about the structure-activity relationship: 1) the activity decreased following the pattern of the -carboline core substitution N-9 > O-7 > O6 > C-3 > C-1, 2) hybrids containing aminoethylene linker (compounds 6-8) exerted more pronounced antimalarial activity.

malaria, hybrid molecules, harmine, chloroquine

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