title: 3D-QSAR Study on dihydro-1,3,5-triazines and their spiro derivatives as DHFR inhibitors by comparative molecular field analysis (CoMFA).
abstract: A 3D-QSAR/CoMFA was performed for a series of triazine and its spiro derivative based DHFR inhibitors displaying IC(50) values ranging from 0.002 to 58.8 μM. Analyses resulted in a reliable computational model with the parameters of n=46, r(2)=0.986, q(2)=0.724, SE=0.164, F=275.889. It is shown that the steric and electrostatic properties predicted by CoMFA contours can be related to the DHFR inhibitory activity. The predictive ability of the resultant model was evaluated using a test set comprised of 18 molecules and the results show that the CoMFA model is able to correctly predict the poor inhibitory activities of the compounds in the testing set. This model is a significant guide to trace the features that really matter especially with respect to the design of novel compounds.
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, China. maxwellcn@yahoo.com
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.forename: Guangya
authors.initials: G
authors.lastname: Xiang
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Yap
authors.forename: Wai-Keung
authors.initials: WK
authors.lastname: Chui
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D013141:Spiro Compounds; D014227:Triazines; D013762:Tetrahydrofolate Dehydrogenase