POM analyses of Raltegravir derivatives: A new reflection enlightening the mechanism of HIV-integrase inhibition

Siham Lahsasni, Taibi Ben Hadda, Vijay Masand, Naziyanaz B. Pathan, Ali Parvez, Ismail Warad, Usama Shaheen, Ammar Bader, Mohamad Aljofan

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Petra/Osiris/Molinspiration analysis (POM) is a promising new bioinformatical approach to establish structure and activity correlations. In the present study, we have reported the POM analyses of Raltegravir analogues that have aimed to figure out the structural features of HIV-integrase inhibitory activity. The resulting model exhibited two controllable bidentate O, O-pockets taken into consideration contributions from the steric and electrostatic fields. The POM analysis has provided interesting insights into the understanding the steric and electronic structural requirements for HIV-IN inhibitory activity. Furthermore, all the molecules were subjected to the toxicity assessment using Molinspiration and Osiris calculations. Among the various HIV-IN inhibitors, compound 27 (Raltegravir) displayed optimum drug-like characteristic activity with low toxicity. The mechanism of HIV-integrase inhibition by different Raltegravir derivatives is also discussed. This study also concluded that the bioactivity of DKA analogues should be discussed on the basis of catalytic activity of bimetallic complexes, not just on the basis of DKA or Raltegravir/HIV-integrase interaction.

Original languageEnglish
Pages (from-to)5121-5136
Number of pages16
JournalResearch on Chemical Intermediates
Volume41
Issue number8
DOIs
Publication statusPublished - Aug 2 2015
Externally publishedYes

Keywords

  • Bimetallic system
  • Diketo acid
  • HIV-integrase inhibitors
  • POM (Petra/Osiris/Molinspiration) analysis
  • Raltegravir

ASJC Scopus subject areas

  • Chemistry(all)

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