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

Sara Abdeyazdan; Maryam Mohajeri; Sedigheh Saberi; Mahmoud Mirzaei; Seyed Abdulmajid Ayatollahi; Lotfollah Saghaei; Mustafa Ghanadian

doi:10.5812/ijpr-128379

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

Iran J Pharm Res. 2022 Sep 2;21(1):e128379. doi: 10.5812/ijpr-128379. eCollection 2022 Dec.

Authors

Sara Abdeyazdan^{1

2}, Maryam Mohajeri², Sedigheh Saberi³, Mahmoud Mirzaei⁴, Seyed Abdulmajid Ayatollahi^{2

5}, Lotfollah Saghaei⁶, Mustafa Ghanadian^{1

2}

Affiliations

¹ Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
² Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
³ Department of Mycology and Parasitology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
⁴ Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
⁵ Department of Pharmacognosy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁶ Department of Medicinal Chemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

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-, and ¹³C-NMR spectral data, and the Stoichiometry 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.

Keywords: Antileishmania; Antimony Pentavalent; Flavonoid Synthesis; Kaempferol; Quercetin.