Synthesis and Leishmanicidal Activities of Six Quercetin Derivatives.

BACKGROUND

Today, leishmaniasis is a widespread, infectious parasitic disease caused by spp. Natural-derived compounds are likely to provide a valuable source of new pharmaceuticals, and among them, quercetin derivatives may have antileishmanial effects. The antileishmanial activity of 3,5,7,3',4'-pentahydroxyflavonol (quercetin) derivatives is partly attributed to the position and pKa of phenolic or catechol hydroxyl groups. Therefore, to optimize their leishmanicidal effect, the structural features of quercetin and its derivatives were improved by acylation or alkylation of hydroxyl groups and changing their pKa and consequently their activities.

MATERIALS AND METHODS

In this study, during a regioselective method, quercetin derivatives were synthesized. The structures of synthesized compounds were confirmed by mass, IR, H-, and C-NMR spectral data. The antileishmanial activities of compounds 1-6 were compared with glucantime as the standard drug against promastigotes of using standard cell-based leishmanicidal assay.

RESULTS

In this study, during a regioselective method, two 7-O-quercetin derivatives (5 and 6), and three quercetin acetate derivatives (2, 3, and 4) were synthesized. In detail, the IC values found against were (1) 2.5 ± 0.92; (2) 2.85 ± 0.99; (3) 15.5 ± 1.95; (4) 13.5 ± 3.5; (5) 2.6 ± 0.57; and (6) 1.3 ± 0.35 μM while IC value of glucantime as the standard drug was 88.5 ± 9.47 μM.

CONCLUSIONS

The present study showed an effective antileishmanial activity of quercetin semisynthetic compounds (1-6) against promastigotes of . Among them, quercetin analogs with more lipophilic and iron-chelating activity showed more antiparasite activity.