Synthesis and antileishmanial activity of antimony (V) complexes of hydroxypyranone and hydroxypyridinone ligands

Vafa Sheikhmoradi, Sedigheh Saberi, Lotfollah Saghaei, Nader Pestehchian, Afshin Fassihi

Abstract


A novel series of antimony (V) complexes with the hydroxypyranone and hydroxypyridinone ligands were synthesized and characterized by 1HNMR, FT-IR and electron spin ionization mass spectroscopic (ESI-MS) techniques. The synthesis process involved protection of hydroxyl group followed by the reaction of the intermediate with primary amines and finally deprotection. All compounds were evaluated for in vitro activities against the amastigote and promastigote forms of Leishmania major. Most of the synthesized compounds exhibited good antileishmanial activity against both forms of L. major. IC50 values of the most active compounds; 9d, 9d and 9e, after 24, 48 and 72 h against amastigote model were 15, 12.5 and 5.5 µg/mL, respectively. 9e, 11 and 9e inhibited the promastigote form of parasite after 24, 48 and 72 h with IC50 values of 10, 2 and 1 µg/mL, respectively.


Keywords


Antileishmania; Sb (V) complexes; Hydroxypyranone; Hydroxypyridinone

Full Text:

PDF

References


Soflaei S, Dalimi A, Ghaffarifar F, Shakibaie M, Shahverdi AR, Shafiepour M. In vitro antiparasitic and apoptotic effects of antimony sulfide nanoparticles on Leishmania infantum. J Parasitol Res. 2012;2012:1–7.

Séby F, Gleyzes C, Grosso O, Plau B, Donard O. Speciation of antimony in injectable drugs used for leishmaniasis treatment (Glucantime®) by HPLC-ICP-MS and DPP. Anal Bioanal Chem. 2012;404(10):2939-2948.

Lessa JA, Reis DC, Mendes IC, Speziali NL, Rocha LF, Pereira VR, et al. Antimony (III) complexes with pyridine-derived thiosemicarbazones: structural studies and investigation on the antitrypanosomal activity. Polyhedron. 2011;30(2):372-380.

Sun H, Yan SC, Cheng WS. Interaction of antimony tartrate with the tripeptide glutathione. Eur J Biochem. 2000;267(17):5450-5457.

Fernandes FR, Ferreira WA, Campos MA, Ramos GS, Kato KC, Almeida GG, et al. Amphiphilic antimony (V) complexes for oral treatment of visceral leishmaniasis. Antimicrob Agents Chemother. 2013;57(9):4229-4236.

Brotherton M-C, Bourassa S, Légaré D, Poirier GG, Droit A, Ouellette M. Quantitative proteomic analysis of amphotericin B resistance in Leishmania infantum. Int J Parasitol Drugs Drug Resist. 2014;4(2):126-132.

Ge R, Sun H. Bioinorganic chemistry of bismuth and antimony: target sites of metallodrugs. Acc Chem Res. 2007;40(4):267-274.

Frézard F, Demicheli C, Kato KC, Reis PG, Lizarazo-Jaimes EH. Chemistry of antimony-based drugs in biological systems and studies of their mechanism of action. Rev Inorg Chem. 2013;33(1):1-12.

Caballero AB, Salas JM, Sánchez-Moreno M. Metal-based therapeutics for leishmaniasis. leishmaniasis-trends in epidemiology, diagnosis and treatment. In Tech. 2014;465-493.

Li DF, Hu PP, Liu MS, Kong XL, Zhang JC, Hider RC, et al. Design and synthesis of hydroxypyridinone-L-phenylalanine conjugates as potential tyrosinase inhibitors. J Agric Food Chem. 2013;61(27):6597-6603.

Dehkordi LS, Liu ZD, Hider RC. Basic 3-Hydroxypyridin-4-ones: Potential antimalarial agents. Eur J Med Chem. 2008;43(5):1035-1047.

Rostami M, Sirous H, Zabihollahi R, Aghasadeghi MR, Sadat SM, Namazi R, et al. Design, synthesis and anti-HIV-1 evaluation of a series of 5-hydroxypyridine-4-one derivatives as possible integrase inhibitors. Med Chem Res. 2015;24(12):4113-4127.

Chen YL, Barlow DJ, Kong XL, Ma YM, Hider RC. Prediction of 3-hydroxypyridin-4-one (HPO) log K 1 values for Fe (iii). Dalton Trans. 2012;41(35):10784-10791.

Ferreira WA, Islam A, Andrade APS, Fernandes FR, Frézard F, Demicheli C. Mixed antimony (v) complexes with different sugars to modulate the oral bioavailability of pentavalent antimonial drugs. Molecules. 2014;19(5):5478-5489.

Demicheli C, Ochoa R, Silva Lula I, Gozzo FC, Eberlin MN, Frézard F. Pentavalent organoantimonial derivatives: two simple and efficient synthetic methods for meglumine antimonate. Appl Organomet Chem. 2003;17(4):226-231.

Tahghighi A, Marznaki FR, Kobarfard F, Dastmalchi S, Mojarrad JS, Razmi S, et al. Synthesis and antileishmanial activity of novel 5-(5-nitrofuran-2-y1)-1, 3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents. Eur J Med Chem. 2011;46(6):2602-2608.

Jacomini AP, Silva MJ, Silva RG, Gonçalves DS, Volpato H, Basso EA, et al. Synthesis and evaluation against Leishmania amazonensis of novel pyrazolo [3, 4-d] pyridazinone-N-acylhydrazone-(bi) thiophene hybrids. Eur J Med Chem. 2016;124:340-349.

Tahghighi A, Razmi S, Mahdavi M, Foroumadi P, Ardestani SK, Emami S, et al. Synthesis and anti-leishmanial activity of 5-(5-nitrofuran-2-yl)-1, 3, 4-thiadiazol-2-amines containing N-[(1-benzyl-1H-1, 2, 3-triazol-4-yl) methyl] moieties. Eur J Med Chem. 2012;50:124-128.

Saberi S, Arjmand R, Soleimanifard S, Khamesipour A, Hosseini SM, Salehi M, et al. In vivo/in vitro immune responses to L. major isolates from patients with no clinical response to Glucantime. Adv Biomed Res. 2016;5.126-131

Ngure PK, Tonui WK, Ingonga J, Mutai C, Kigondu E, Ngrsquo Z, et al. In vitro antileishmanial activity of extracts of Warburgia ugandensis (Canellaceae), a Kenyan medicinal plant. J Med Plants Res. 2009;3(2):061-066.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.