engleski

Antiplasmodial Activity of SAHAquines, Novel SAHA - Primaquine Hybrids

SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and primaquine, an antimalarial drug with low antiproliferative activity (1-3). The prepared SAHAquines differ in linker length/type and/or functional groups: compounds 1 are esters, 2 are carboxylic acids, 4 are unsubstituted and 3 and 5 are O-benzyl and O-methyl substituted hydroxamic acids. To evaluate their antiplasmodial activity, SAHAquines were tested in vitro against P. falciparum erythrocytic stages (3D7 and Dd2 strains) and against P. berghei hepatic stages. Overall, our results show that SAHAquines with free hydroxamic acid were the most potent, out of which SAHAquine 4b had the lowest IC50 values (0.4 μM for Pf3D7, 1.9 μM for the PfDd2 strain (erythrocytic stage) and 0.43 μM (hepatic stage)). SAHAquine 1b from the ester subclass was the only compound out of hydroxamic acid series with IC50 values in a low micromolar range. This is probably due to α, β-unsaturated carbonyl group (Michael acceptor moiety), capable of conjugate addition.

malaria ; antiplasmodial activity ; primaquine ; vorinostat ; hybrid drugs

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