Author/Authors :
Faghihi, Kamyar Department of Pharmaceutical Chemistry - Faculty of Pharmaceutical Chemistry - Tehran Medical Sciences, Islamic Azad University, Tehran, Iran , Safakish, Mahdieh Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Zebardast, Tannaz Department of Pharmaceutical Chemistry - Faculty of Pharmaceutical Chemistry - Tehran Medical Sciences, Islamic Azad University, Tehran, Iran , Hajimahdi, Zahra Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Zarghi, Afshin Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract :
A series of 2-benzoxazolinone, diazocoumarin and quinazoline derivatives have been
shown to inhibit HIV replication in cell culture. To understand the pharmacophore properties of
selected molecules and design new anti-HIV agents, quantitative structure–activity relationship
(QSAR) study was developed using a descriptor selection approach based on the stepwise
method. Multiple linear regression method was applied to relate the anti-HIV activities
of dataset molecules to the selected descriptors. Obtained QSAR model was statistically
significant with correlation coefficient R2 of 0.84 and leave one out coefficient Q2 of 0.73. The
model was validated by test set molecules giving satisfactory prediction value (R2
test) of 0.79.
Molecules also were docked on HIV integrase enzyme and showed important interactions with
the key residues in enzyme active site. These data might be helpful for design and discovery
of novel anti-HIV compounds.
Keywords :
Stepwise , Multiple linear regressions , QSAR , Anti-HIV , Docking
