Investigation of dual anti-HIV/HSV activity of oxoquinoline-acylhydrazone derivatives by molecular docking

Someoxoquinoline-acylhydrazonederivativesshowedactivityagainst HumanImmunodeficiency Virus type 1 (HIV-1). These compounds must also be active against Herpes Simplex Virus type 1 (HSV-1) by an inhibition mechanism where they interact with the HSV-DNA-polymerase/DNA-duplex complex. There are several...

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Detalhes bibliográficos
Autores: Silva, Yuri Inácio Marques, Yoneda, Julliane
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Brasil
Recursos:Universidade de São Paulo (USP)
Repositorio:Brazilian Journal of Pharmaceutical Sciences
Idioma:inglés
OAI Identifier:oai:revistas.usp.br:article/227838
Acesso em linha:https://www.revistas.usp.br/bjps/article/view/227838
Access Level:acceso abierto
Palavra-chave:Molecular docking
HIV-1
HSV-1
Oxoquinoline-acylhydrazone derivatives
Dual inhibitors
Descrição
Resumo:Someoxoquinoline-acylhydrazonederivativesshowedactivityagainst HumanImmunodeficiency Virus type 1 (HIV-1). These compounds must also be active against Herpes Simplex Virus type 1 (HSV-1) by an inhibition mechanism where they interact with the HSV-DNA-polymerase/DNA-duplex complex. There are several treatment options for HSV-1 but there is no cure for the disease, which may represent a life risk for individuals co-infected with HIV. In this work molecular docking studies were carried out in an attempt to understand the dual activity of these oxoquinoline-acyhydrazone derivatives. The compounds were docked in two possible situations: (i) in the polymerase domain of HIV-1 Reverse Transcriptase (RT) enzyme in order to verify whether the inhibition occurs similarly to the proposed mechanism for HSV-1 inhibition, where the ligand would form a complex with the enzyme and the DNA; (ii) in the allosteric site of RT in order to verify if the inhibition occur in a similar way to non-nucleoside RT inhibitors (NNRTI). The studied compounds showed higher binding affinity to the allosteric site of RT and the results indicate that the inhibition should occur in a mechanism similar to that of NNRTI, which produces an allosteric inhibition that induces structural changes in the enzymatic active site.