Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2

Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2 Publisher Pubmed

Navidpour L¹ ; Lima ML² ; Milne R² ; Wyllie S² ; Hadjesfandiari N¹ ; Choudhary MI³ ; Khan S³ ; Yousuf S³

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1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2. Division of Biological Chemistry and Drug Discovery, Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom
3. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

Source: Antimicrobial Agents and Chemotherapy Published:2022

Abstract

The antileishmanial activity of a series of (Z)-2-(heteroarylmethylene)-3(2H)- benzofuranone derivatives, possessing 5-nitroimidazole or 4-nitroimidazole moieties, was investigated against Leishmania major promastigotes and some analogues exhibited prominent activities. Compounds with IC50 values lower than 20 mM were further examined against L. donovani axenic amastigotes. Evaluated analogues in 5-nitroimidazole subgroup demonstrated significantly superior activity (;17-88-folds) against L. donovani in comparison to L. major. (Z)-7-Methoxy-2-(1-methyl-5-nitroimidazole-2-ylmethylene)-3 (2H)-benzofuranone (5n) showed the highest L. donovani anti-axenic amastigote activity with IC50 of 0.016 mM. The cytotoxicity of these analogues was determined using PMM peritoneal mouse macrophage and THP-1 human leukemia monocytic cell lines and high selectivity indices of 26 to 431 were obtained for their anti-axenic amastigote effect over the cytotoxicity on PMM cells. Further studies on their mode of action showed that 5-nitroimidazole compounds were bioactivated predominantly by nitroreductase 1 (NTR1) and 4-nitroimidazole analogues by both NTR1 and 2. It is likely that this bioactivation results in the production of nitroso and hydroxylamine metabolites that are cytotoxic for the Leishmania parasite. © 2022 American Society for Microbiology.

2. Development of Topical Liposomes Containing Miltefosine for the Treatment of Leishmania Major Infection in Susceptible Balb/C Mice, Acta Tropica (2019)

3. In Vitro and in Vivo Anti-Parasitic Activity of Biogenic Antimony Sulfide Nanoparticles on Leishmania Major (Mrho/Ir/75/Er), Parasitology Research (2019)

4. Sambucus Ebulus Extract Stimulates Cellular Responses in Cutaneous Leishmaniasis, Parasite Immunology (2019)

5. Development of a Topical Liposomal Formulation of Amphotericin B for the Treatment of Cutaneous Leishmaniasis, International Journal for Parasitology: Drugs and Drug Resistance (2019)

6. The Role of Glcnac-Pi-De-N-Acetylase Gene by Gene Knockout Through Homologous Recombination and Its Consequences on Survival, Growth and Infectivity of Leishmania Major in in Vitro and in Vivo Conditions, Acta Tropica (2016)

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Style	Citing Format
MLA	Navidpour L, et al.. "Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2." Antimicrobial Agents and Chemotherapy, vol. 66, no. 11, 2022, pp. -.
APA	Navidpour L, Lima ML, Milne R, Wyllie S, Hadjesfandiari N, Choudhary MI, Khan S, Yousuf S (2022). Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2. Antimicrobial Agents and Chemotherapy, 66(11), -.
Chicago	Navidpour L, Lima ML, Milne R, Wyllie S, Hadjesfandiari N, Choudhary MI, Khan S, Yousuf S. "Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2." Antimicrobial Agents and Chemotherapy 66, no. 11 (2022): -.
Harvard	Navidpour L et al. (2022) 'Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2', Antimicrobial Agents and Chemotherapy, 66(11), pp. -.
Vancouver	Navidpour L, Lima ML, Milne R, Wyllie S, Hadjesfandiari N, Choudhary MI, et al.. Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2. Antimicrobial Agents and Chemotherapy. 2022;66(11):-.
BibTex	@article{ author = {Navidpour L and Lima ML and Milne R and Wyllie S and Hadjesfandiari N and Choudhary MI and Khan S and Yousuf S}, title = {Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2}, journal = {Antimicrobial Agents and Chemotherapy}, volume = {66}, number = {11}, pages = {-}, year = {2022} }
RIS	TY - JOUR AU - Navidpour L AU - Lima ML AU - Milne R AU - Wyllie S AU - Hadjesfandiari N AU - Choudhary MI AU - Khan S AU - Yousuf S TI - Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3 (2H)-Benzofuranones: Synthesis, in Vitro Assessment, and Bioactivation by Ntr 1 and 2 JO - Antimicrobial Agents and Chemotherapy VL - 66 IS - 11 SP - EP - PY - 2022 ER -

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