A new series of 2,4-thiazolidinediones endowed with potent aldose reductase inhibitory activity

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SEVER B., ALTINTOP M. D., Demir Y., TÜRKEŞ C., Ozbas K., AKALIN ÇİFTÇİ G., ...More

OPEN CHEMISTRY, vol.19, no.1, pp.347-357, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 1
  • Publication Date: 2021
  • Doi Number: 10.1515/chem-2021-0032
  • Journal Name: OPEN CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.347-357
  • Keywords: aldose reductase, thiazolidinedione, cytotoxicity, molecular docking, IN-SILICO, CARBONIC-ANHYDRASE, DERIVATIVES, VITRO, ACETYLCHOLINESTERASE, COMPLICATIONS, INSIGHTS, TARGETS, DESIGN
  • Anadolu University Affiliated: Yes


In an effort to identify potent aldose reductase (AR) inhibitors, 5-(arylidene)thiazolidine-2,4-diones (1-8), which were prepared by the solvent-free reaction of 2,4-thiazolidinedione with aromatic aldehydes in the presence of urea, were examined for their in vitro AR inhibitory activities and cytotoxicity. 5-(2-Hydroxy-3-methylbenzylidene)thiazolidine-2,4-dione (3) was the most potent AR inhibitor in this series, exerting uncompetitive inhibition with a K-i value of 0.445 +/- 0.013 mu M. The IC50 value of compound 3 for L929 mouse fibroblast cells was determined as 8.9 +/- 0.66 mu M, pointing out its safety as an AR inhibitor. Molecular docking studies suggested that compound 3 exhibited good affinity to the binding site of AR (PDB ID: 4JIR). Based upon in silico absorption, distribution, metabolism, and excretion data, the compound is predicted to have favorable pharmacokinetic features. Taking into account the in silico and in vitro data, compound 3 stands out as a potential orally bioavailable AR inhibitor for the management of diabetic complications as well as nondiabetic diseases.