ScienceAsia 30 (2004): 81-88 |doi: 10.2306/scienceasia1513-1874.2004.30.081
3D-QSAR Studies on Phthalimide Derivatives as HIV-1
Reverse Transcriptase Inhibitors
Weerasak Samee,a Jiraporn Ungwitayatorn,b,* Chutima Matayatsukb and Jutarat Pimthonb
ABSTRACT: The novel non-nucleoside HIV-1 reverse transcriptase inhibitors in a phthalimide series were
subjected to the three-dimensional quantitative structure-activity relationship (3D QSAR) studies using
comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis
(CoMSIA). The best predictive CoMFA model gave cross-validated r2 (q2) = 0.688, non-cross-validated r2 =
0.996, included the highest occupied molecular orbital (HOMO) energies in addition to CoMFA fields, and
the best predictive CoMSIA model has q2 = 0.629, non-cross-validated r2 = 0.994, included steric, electrostatic,
hydrophobic and hydrogen bond acceptor fields. A test set of 12 compounds was used to determine the
predictive value of the models. The calculated (predicted) and experimental inhibitory activities were well
correlated. The analysis of the 3D contour maps from both CoMFA and CoMSIA models offer important
structural insight into designing novel and more active compounds prior to their synthesis.
a Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok, 26120, Thailand.
b Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya, Bangkok 10400, Thailand.
* Corresponding author, E-mail: email@example.com
Received 18 Jul 2003,
Accepted 17 Nov 2003