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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

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

Journal

Title: Journal of Molecular Graphics and Modelling

Vol. 44

Pages: 91-103

ISSN: 1093-3263

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 1 Citation

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13