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Phenotypic investigation of 4-nitrophenylacetyl- and 4-nitro-1H-imidazoyl-based compounds as antileishmanial agents

Published online by Cambridge University Press:  03 February 2022

Camila C. Santos ,
Huaisheng Zhang ,
Marcos M. Batista ,
Gabriel M. de Oliveira ,
Kelly C. Demarque ,
Natália L. da Silva ,
Otacílio C. Moreira ,
Ifedayo Victor Ogungbe  and
Maria de Nazaré Correia Soeiro Open the ORCID record for Maria de Nazaré Correia Soeiro [Opens in a new window]
Camila C. Santos
Affiliation:
Laboratory of Cellular Biology (LBC), Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
Huaisheng Zhang
Affiliation:
Department of Chemistry, Jackson State University, Jackson, MS 39217-0510, USA
Marcos M. Batista
Affiliation:
Laboratory of Cellular Biology (LBC), Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
Gabriel M. de Oliveira
Affiliation:
Laboratory of Cellular Biology (LBC), Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
Kelly C. Demarque
Affiliation:
Laboratory of Cellular Biology (LBC), Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
Natália L. da Silva
Affiliation:
Laboratory of Molecular Biology and Endemic Diseases, Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
Otacílio C. Moreira
Affiliation:
Laboratory of Molecular Biology and Endemic Diseases, Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
Ifedayo Victor Ogungbe*
Affiliation:
Department of Chemistry, Jackson State University, Jackson, MS 39217-0510, USA
Maria de Nazaré Correia Soeiro*
Affiliation:
Laboratory of Cellular Biology (LBC), Oswaldo Cruz Institute (IOC/FIOCRUZ), 21040-360 Rio de Janeiro, RJ, Brazil
*
Authors for correspondence: Ifedayo Victor Ogungbe, E-mail: [email protected]; Maria de Nazaré Correia Soeiro, E-mail: [email protected]
Authors for correspondence: Ifedayo Victor Ogungbe, E-mail: [email protected]; Maria de Nazaré Correia Soeiro, E-mail: [email protected]
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Abstract

Cutaneous leishmaniasis (CL) is a spectrum of clinical manifestations characterized by severe skin ulcerations that leads to social stigma. There are limited treatment options for CL, and the available drugs are becoming less efficacious due to drug resistance. More efficacious and safer antileishmanial drugs are needed. In this study, the biological effect of seven synthetically accessible nitroaromatic compounds was evaluated in vitro against amastigotes of Leishmania amazonensis, followed by in vivo evaluation using mouse models of CL. Two compounds (6 and 7) were active against amastigotes in vitro [half-maximal effective concentration (EC50): 4.57 ± 0.08 and 9.19 ± 0.68 μm, respectively], with selectivity indexes >50, and the other compounds were not selective. In vivo, compounds 6 and 7 (10 mg kg−1, twice a day for 14 days) failed to reduce skin lesion sizes and parasite loads determined by light microscopy of lesion imprints and quantitative polymerase chain reaction. Nevertheless, the in vitro leishmanicidal efficacy sustained their use as templates for nitroimidazole-based antileishmanial drug discovery programmes focusing on analogues with more suitable properties.

Keywords

Cutaneous leishmaniasisin vitro experimental chemotherapyin vivoLeishmania amazonensisshape-based virtual screening
Type
Research Article
Information
Parasitology , Volume 149 , Issue 4 , April 2022 , pp. 490 - 495
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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