Sb(V) Kaempferol and Quercetin Derivative Complexes: Synthesis, Characterization and Antileishmanial Activities Publisher



Abdeyazdan S^{1, 2} ; Mohajeri M² ; Saberi S³ ; Mirzaei M⁴ ; Ayatollahi SA^{2, 5} ; Saghaei L⁶ ; Ghanadian M^{1, 2} Show Affiliations
Source: Iranian Journal of Pharmaceutical Research Published:2022

Abstract

Background: Recent studies on Leishmaniasis treatment have confirmed the antiparasitic effects of flavonols and organic antimony pentavalent [(Sb(V)] complexes. Objectives: This study aimed to identify new Sb(V) complexes by combining the benefits of antimonials and flavonols as well as by optimizing their properties. Methods: Kaempferol and quercetin peracetate were prepared using acetic anhydride in pyridine. By performing regioselective synthesis, 7-O-paramethylbenzyl as an electron-donating group and 7-O-paranitrobenzyl as an electron-withdrawing group were added to quercetin, and, then, the synthesis of Sb(V) kaempferol and quercetin derivative complexes were performed using SbCl5 solution in glacial acetic acid. The structures were confirmed by UV, ESI mass, IR, 1H-, and13 C-NMR spectral data, and the Stoichiome-try of the ligand-metal complex by the mole ratio method. Computational molecular modeling was conducted using the Gaussian program. Results: The structures were confirmed based on the results from UV, nuclear magnetic resonance (NMR), and electrospray ionization (ESI) mass analyses (3-12). Among the produced compounds, 11 and 12 as newly described, and other compounds as pre-defined compounds were identified. According to the results from biological test, kaempferol triacetate with more lipophilicity showed the highest anti-promastigote activity with an IC50 value of 14.93 ± 2.21 µM. As for anti-amastigote activity, despite the differences, all antimony complexes showed anti-amastigote effects in vitro with IC50 values of 0.52 to 14.50 µM. Conclusions: All flavonol Sb(V) complexes showed higher activity compared to meglumine antimonate in anti-amastigote effect. Inside the host macrophages, by breaking down the complex into antimony and quercetin or kaempferol analogs, the observed antiparasitic effects may have been related to both Sb(V)/Sb(III) conversion and flavonoid antileishmanial activities. © 2022, Author(s).