BioScience Trends. 2012;6(5):234-240. (DOI: 10.5582/bst.2012.v6.5.234)

Density functional theory based quantitative structure-property relationship studies on coumarin-based prodrugs.

Yang XY, Hou XB, Wang BH, Li MY, Fang H


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.

KEYWORDS: Coumarin, prodrug, QSPR, quantitative structure-property relationship, DFT

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