Abstract
The shortage of drugs currently available for the treatment of diabetic complications has aroused our interest for the search of new aldose reductase inhibitors (ARIs) endowed with more favorable biological properties. In response, quantitative structure–activity relationship (QSAR) study has been performed on a series of 5-arylidene-2,4-thiazolidinediones using the Fujita-Ban and the classical Hansch approach and molecular modeling studies employing AM1 calculations to gain structural insight into the binding mode of these molecules to the aldose reductase enzyme. The QSAR models were generated using 18 compounds. The predictive ability of the resulting QSAR models was evaluated employing the leave-one-out method of cross validation. Remarkably, the results obtained from the Fujita-Ban and Hansch approaches were in agreement with the molecular modeling studies. The QSAR analysis reported herein confirms that the presence of the carboxylic anionic head of the N-3 acetic chain is an important, albeit not essential, structural requisite to produce high levels of enzyme inhibition. Furthermore, the hydrophobic substitutions are conducive to this activity.
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Authors are grateful to the Director, Shri G. S. Institute of Technology and Science, Indore for providing facilities for this work.
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Soni, L.K., Gupta, A.K. & Kaskhedikar, S.G. QSAR study of 5-arylidene-2,4-thiazolidinediones as aldose reductase inhibitors. Med Chem Res 17, 258–266 (2008). https://doi.org/10.1007/s00044-007-9061-4
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DOI: https://doi.org/10.1007/s00044-007-9061-4