Quantitative Structure–Activity Relationship Analysis of Some Thiourea Derivatives with Activities Against HIV‐1 (IIIB)
Zuguang Li, Kexian Chen, Haiying Xie, Jianrong Gao · QSAR & Combinatorial Science · 2008
Abstract 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 (r2=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).