Quantitative Structure - Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV-1 (IIIB)

Two-dimensional (2D) and Three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) studies have been carried out on a series of 42 recently synthesized thiourea derivatives to find out the structural requirements of their protection of MT-4 cells against Human Immunodeficiency Virus (HIV)-1 (IIIB). The statistically significant 2D-QSAR model (r(2)=0.897) was developed by Genetic Function Approximation (GFA) when the number of descriptors in equation was set to four, indicating descriptors of S_aaCH, Shadow_XYfrac, Lowest Unoccupied Molecular Orbital (LUMO), and Hydrogen-Bond Acceptors (Hbond Acceptor) mainly control the bioactivity. The validation of the model was done by the full cross-validation tests, randomization tests, and external test set prediction. Molecular Field Analysis (MFA) investigated the substitutional requirements for the favorable receptor-drug interaction and constructed the best 3D-QSAR model using Genetic Partial Least Squares (G/PLS) method, showing that the electrostatic fields contribute significantly toward bioactivity. The results obtained by combining both methodologies give insight into the key features for designing more potent analogs against HIV-1(IIIB).