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Quantitative structure-activity relationship of spirosuccinimide type aldose reductase inhibitors diminishing sorbitol accumulation in vivo

Title
Quantitative structure-activity relationship of spirosuccinimide type aldose reductase inhibitors diminishing sorbitol accumulation in vivo
Author
원호식
Keywords
QSAR; aldose reductase inhibitor; sorbitol accumulation; Caco-2 cell permeability
Issue Date
2006-05
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOORGANIC & MEDICINAL CHEMISTRY, v. 14, No. 9, Page. 3090-3097
Abstract
Racemate physicochemical descriptors are employed to probe the quantitative structure-activity relationship of spirosuccinimide type aldose reductase inhibitors and the in vivo inhibitory activity of sorbitol accumulation. The in vivo activity data include the percent inhibition and ED50 assay results on the literature. The derived QSAR equations show that the hydrophobic character of aldose reductase inhibitor is the major contributing factor to enhance in vivo activity. As the hydrophobicity of compounds is related to both the membrane permeability and the binding affinity to the aldose reductase, its contribution to the pharmacokinetic behavior is further scrutinized by evaluating pK(a) and the Caco-2 cell permeability. The high correlation between ED50 and the Caco-2 cell permeability of in vitro active compounds indicates that the membrane permeability is essential for in vivo efficacy. (c) 2005 Elsevier Ltd. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0968089605012034https://repository.hanyang.ac.kr/handle/20.500.11754/107589
ISSN
0968-0896; 1464-3391
DOI
10.1016/j.bmc.2005.12.019
Appears in Collections:
COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > CHEMICAL AND MOLECULAR ENGINEERING(화학분자공학과) > Articles
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