title: Density functional theory based quantitative structure-property relationship studies on coumarin-based prodrugs.
abstract: A coumarin-based prodrug system plays a significant role in preparing esterase-sensitive prodrugs of amines and peptides. The electronic structures of 27 coumarin-based prodrugs developed in our lab were calculated at a B3LYP/6-31+G (d,p) level with a Gaussian 03 program. The calculated structural parameters were taken as theoretical descriptors to establish five novel QSPR models. The SMLR linear model (q² = 0.427, r² = 0.516) and the PLS linear model (q² = 0.584, r² = 0.663) were developed with descriptors selected by an Unsupervised Forward Selection method. Another three nonlinear QSPR models were established by a Polynomial Neural Network (PNN) Simulation method (q² = 0.692, 0.675, 0.663; r² = 0.700, 0.688, 0.672). We suggest that the QSPR models derived here, especially the PNN models, can be used to predict the release kinetics of coumarin-based prodrugs as well as design new derivatives of coumarin-based prodrug candidates.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology-Ministry of Education, School of Pharmacy, Shandong University, Ji'nan, Shandong, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Yang
authors.forename: Xuben
authors.initials: X
authors.lastname: Hou
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
mesh_terms: D003374:Coumarins / Q000737:chemistry*; D008962:Models, Theoretical; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D003374:Coumarins; D011355:Prodrugs; C030123:coumarin