Is the conformational flexibility of piperazine derivatives important to inhibit HIV-1 replication?

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Catia Teixeira (Autor) Outra; Serradji, N (Autor) Outra; Amroune, S (Autor) Outra; Storck, K (Autor) Outra; Rogez Kreuz, C (Autor) Outra; Clayette, P (Autor) Outra; Barbault, F (Autor) Outra; Maurel, F (Autor) Outra

Revista

Título: Journal of Molecular Graphics and Modelling

Vol. 44

Páginas: 91-103

ISSN: 1093-3263

Editora: Elsevier

Indexação

ISI Web of Knowledge - 3 Citações

Scopus - 1 Citação

Outras Informações

ID Authenticus: P-006-9A3

DOI: 10.1016/j.jmgm.2013.05.003

Abstract (EN): The conserved binding site of HIV-1 gp120 envelope protein, an essential component in the viral entry process, provides an attractive antiviral target. The structural similarities between two piperazine derivatives: PMS-601, showing a dual activity for anti-PAF and anti-HIV activity, and BMS-378806, known to inhibit HIV-1 gp120, motivated us to merge important structural features of the two compounds. Novel piperazine derivatives were synthesized and evaluated in vitro concerning their ability to inhibit HIV-1 replication in in vitro infected lymphocytes. We described an approach that combines molecular docking, molecular dynamics, MM-PBSA calculations and conformational analysis to rationally predict piperazine derivatives binding mode with HIV-1 gp120. We also inquired about the conformational adaptability of the molecules, upon complex formation, and its importance to their respective inhibitory activity. The analysis suggested that the impact of the flexibility of these molecules revealed to be more important, in the context of drug design, than it has generally been assumed. These new insights at the atomic level might be useful to design inhibitors with improved antiviral activity.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13