TY - JOUR
T1 - POM analyses of Raltegravir derivatives
T2 - A new reflection enlightening the mechanism of HIV-integrase inhibition
AU - Lahsasni, Siham
AU - Ben Hadda, Taibi
AU - Masand, Vijay
AU - Pathan, Naziyanaz B.
AU - Parvez, Ali
AU - Warad, Ismail
AU - Shaheen, Usama
AU - Bader, Ammar
AU - Aljofan, Mohamad
PY - 2015/8/2
Y1 - 2015/8/2
N2 - 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.
AB - 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.
KW - Bimetallic system
KW - Diketo acid
KW - HIV-integrase inhibitors
KW - POM (Petra/Osiris/Molinspiration) analysis
KW - Raltegravir
UR - http://www.scopus.com/inward/record.url?scp=84934435628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84934435628&partnerID=8YFLogxK
U2 - 10.1007/s11164-014-1616-7
DO - 10.1007/s11164-014-1616-7
M3 - Article
AN - SCOPUS:84934435628
VL - 41
SP - 5121
EP - 5136
JO - Research on Chemical Intermediates
JF - Research on Chemical Intermediates
SN - 0922-6168
IS - 8
ER -