Abstract
Quantitative structure-activity relationship analysis of some recently synthesized thiourea derivatives was studied for their cytotoxicity data (CC50) in MT-4 cells. The statistically significant 2D-QSAR model-1 (r2 = 0.964, r2 CV = 0.943 and r2 -pred = 0.961) constructed by genetic function approximation (GFA) methodology was obtained when the number of descriptors was set to 4, indicating that the descriptors of the lowest unoccupied orbital energy (LUMO), radius of gyration (RadOfGyration) and E-state indices (S_ssCH2 and S_aaCH) crucially contributed to biological activity. The validation of the model was done by full cross-validation tests, randomization tests and external test set prediction. Molecular field analysis (MFA) on the corresponding training set investigated the substitutional requirements for the favorable receptor-drug interaction using genetic partial least squares (G/PLS) method, showing that both steric and electrostatic fields play a major role in determining activity. The results derived by combining both methodologies may be useful in further prediction of cytotoxity data (CC50) of corresponding anti-HIV drugs.
Keywords: Genetic function approximation, Molecular field analysis, Quantitative structure-activity relationship, Anti-HIV activity, Thiourea derivatives
Letters in Drug Design & Discovery
Title: Quantitative Structure-Activity Relationship Studies on Some Novel Anti- HIV Thiourea Derivatives with Cytotoxicity Data (CC50) in MT-4 Cells
Volume: 6 Issue: 3
Author(s): Ke-Xian Chen, Zu-Guang Li, Hai-Ying Xie and Jian-Rong Gao
Affiliation:
Keywords: Genetic function approximation, Molecular field analysis, Quantitative structure-activity relationship, Anti-HIV activity, Thiourea derivatives
Abstract: Quantitative structure-activity relationship analysis of some recently synthesized thiourea derivatives was studied for their cytotoxicity data (CC50) in MT-4 cells. The statistically significant 2D-QSAR model-1 (r2 = 0.964, r2 CV = 0.943 and r2 -pred = 0.961) constructed by genetic function approximation (GFA) methodology was obtained when the number of descriptors was set to 4, indicating that the descriptors of the lowest unoccupied orbital energy (LUMO), radius of gyration (RadOfGyration) and E-state indices (S_ssCH2 and S_aaCH) crucially contributed to biological activity. The validation of the model was done by full cross-validation tests, randomization tests and external test set prediction. Molecular field analysis (MFA) on the corresponding training set investigated the substitutional requirements for the favorable receptor-drug interaction using genetic partial least squares (G/PLS) method, showing that both steric and electrostatic fields play a major role in determining activity. The results derived by combining both methodologies may be useful in further prediction of cytotoxity data (CC50) of corresponding anti-HIV drugs.
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Chen Ke-Xian, Li Zu-Guang, Xie Hai-Ying and Gao Jian-Rong, Quantitative Structure-Activity Relationship Studies on Some Novel Anti- HIV Thiourea Derivatives with Cytotoxicity Data (CC50) in MT-4 Cells, Letters in Drug Design & Discovery 2009; 6 (3) . https://dx.doi.org/10.2174/157018009787847828
DOI https://dx.doi.org/10.2174/157018009787847828 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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