Leishmanicidal activity and 4D quantitative structure–activity relationship and molecular docking studies of vanillin-containing 1,2,3-triazole derivatives-Reference-Cited by-同舟云学术

Leishmanicidal activity and 4D quantitative structure–activity relationship and molecular docking studies of vanillin-containing 1,2,3-triazole derivatives

Published:2024-01 Issue:2 Volume:16 Page:139-155
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Rodrigues Gazolla Poliana Aparecida¹^ORCID,Lima Wallace Pacienza²^ORCID,de Aguiar Alex Ramos¹^ORCID,Gonçalves Borsodi Maria Paula³^ORCID,Costa Adilson Vidal⁴^ORCID,de Oliveira Fabrício Marques⁵^ORCID,de Oliveira Osmair Vital⁶^ORCID,Andreazza Costa Maria Cristina⁷^ORCID,Castro Ferreira Marcia Miguel⁷^ORCID,do Nascimento Cláudia Jorge⁸^ORCID,Junker Jochen⁹^ORCID,Vaz Boniek Gontijo¹⁰^ORCID,Teixeira Róbson Ricardo¹^ORCID

Affiliation:

1. Grupo de Pesquisa e Síntese de Compostos Bioativos (GSPCB), Departamento de Química, Universidade Federal de Viçosa, Viçosa-MG, 36570-900, Brazil

2. Escola de Ciências da Saúde, Universidade do Grande Rio, Rio de Janeiro-RJ, 22775-003, Brazil

3. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil

4. Departamento de Química e Física, Universidade Federal do Espírito Santo, Alegre-ES, 29500-000, Brazil

5. Instituto Federal de Minas Gerais (IFMG), Campus Ouro Branco, Ouro Branco-MG, 36494-018, Brazil

6. Instituto Federal de São Paulo – Campus Catanduva, Catanduva-SP, 15808-305, Brazil

7. Instituto de Química, Universidade Estadual de Campinas, Campinas-SP, 13083-970, Brazil

8. Departamento de Ciências Naturais, Instituto de Biociências, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro-RJ, 22290-240, Brazil

9. Centro de Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro-RJ, 21040-361, Brazil

10. Instituto de Química, Universidade Federal de Goiás, Goiânia-GO, 74001-970, Brazil

Abstract

Aim: The assessment of the antileishmanial potential of 22 vanillin-containing 1,2,3-triazole derivatives against Leishmania braziliensis is reported. Materials & methods: Initial screening was performed against the parasite promastigote form. The most active compound, 4b, targeted parasites within amastigotes (IC50 = 4.2 ± 1.0 μmol l-1), presenting low cytotoxicity and a selective index value of 39. 4D quantitative structure–activity relationship and molecular docking studies provided insights into structure–activity and biological effects. Conclusion: A vanillin derivative with significant antileishmanial activity was identified. Enhanced activity was linked to increased electrostatic and Van der Waals interactions near the benzyl ring of the derivatives. Molecular docking indicated the inhibition of the Leishmania amazonensis sterol 14α-demethylase, using Leishmania infantum sterol 14α-demethylase as a model, without affecting the human isoform. Inhibition was active site competition with lanosterol.

Funder

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

Publisher

Informa UK Limited

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2023-0246

Reference75 articles.

1. Leishmaniasis: the act of transmission

2. Leishmaniasis

3. Cutaneous and mucocutaneous leishmaniasis

4. Leishmaniasis Worldwide and Global Estimates of Its Incidence