Exploring MIA-QSARs for farnesyltransferase inhibitory effect of antimalarial compounds refined by docking simulations  

作　　者：Omar Deeb Sherin Alfalah Matheus P. Freitas Elaine F. F. da Cunha Teodorico C. Ramalho 

机构地区：[1]Faculty of Pharmacy, Al-Quds University, Jerusalem, Palestine

出　　处：《Journal of Biophysical Chemistry》2012年第1期58-71,共14页生物物理化学（英文）

摘　　要：Two series of farnesyltransferase (FTase) inhibitors were grouped and their antimalarial activi-ties modeled by means of multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR). A reliable model was achieved, with r2 for calibration, external prediction and leave-one-out cross-validation of 0.96, 0.87 and 0.83, respectively. Therefore, biological activities of congeners can be estimated using the QSAR model. The bioactivities of new compounds based on the miscellany of substructures of the two classes of FTase inhibitors were predicted using the MIA-QSAR model and the most promising ones were submitted to ADME (absorption, distribution, metabolism and excretion) and docking evaluation. Despite the smaller interaction energy of the two most promising, predicted compounds in comparison to the two most active compounds of the data set, one of the proposed structures did not violate any Lipinski’s rule of five. Therefore, it is either a potential drug or may drive synthesis of similar, improved compounds.Two series of farnesyltransferase (FTase) inhibitors were grouped and their antimalarial activi-ties modeled by means of multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR). A reliable model was achieved, with r2 for calibration, external prediction and leave-one-out cross-validation of 0.96, 0.87 and 0.83, respectively. Therefore, biological activities of congeners can be estimated using the QSAR model. The bioactivities of new compounds based on the miscellany of substructures of the two classes of FTase inhibitors were predicted using the MIA-QSAR model and the most promising ones were submitted to ADME (absorption, distribution, metabolism and excretion) and docking evaluation. Despite the smaller interaction energy of the two most promising, predicted compounds in comparison to the two most active compounds of the data set, one of the proposed structures did not violate any Lipinski’s rule of five. Therefore, it is either a potential drug or may drive synthesis of similar, improved compounds.

关 键 词：ADMET Docking FARNESYLTRANSFERASE Inhibitors Malaria Multivariate Image Analysis-QSAR 

分 类 号：R73[医药卫生—肿瘤]