Design, Synthesis, and Molecular Docking Studies of Integrated Benzylidenethiazolidine‐2,4‐Dione and Thieno[2,3‐d]pyrimidine‐6‐Carboxylate Derivatives as Potent Antidiabetic agents

• Published in: ChemistrySelect (Weinheim) Vol. 8; no. 48
• Main Authors: Nagaraju, Begari, Rajeswari, Muthirevula, Vedasree, Nalluri, Rao, Chippada Appa, Srinivasa, Vulichi R., Prabha, Thangavelu, Rao, Chunduri Venkata, Maddila, Suresh
• Format: Journal Article
• Language: English
• Published: 22-12-2023
• Subjects: Anti-diabetic; Antioxidant; Benzylidenethiazolidine; Synthesis; Thieno-pyrimidine
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202303786

The present work describes the synthesis of new series of 5‐arylidene‐thiazolidine‐2,4‐dione, thieno[2,3‐d]pyrimidine‐6‐carboxylate derivatives 9 a–o. A variety of spectroscopic techniques like IR, 13CNMR, 1HNMR and LCMS were used to establish the presence of the every synthesized scaffold. The antioxidant activity of the target compounds has been studied by three different methods indicated the significant DPPH, NO and H2O2. Further, all the derivatives were evaluated for the in vitro antidiabetic potential against human pancreatic α‐amylase (PDB ID: 5NN3) and human lysosomal acid α‐glucosidase (PDB ID: 2QV4) enzymes followed by Molecular docking studies to ascertain the binding interactions of the compounds with the enzymes. The compounds 9 b and 9 g containing methoxy groups were found to exhibit potent antidiabetic and antioxidant activity. Therefore, it was rationalized that two privileged pharmacophores i. e. aryledenethiazolidine‐2,4‐dione and thieno[2,3‐d]pyrimidine‐6‐carboxylate assimilated hybrids, may be beneficial as lead template for the advance of future anti‐diabetic agents. Thus, benzylidenethiazolidine‐2,4‐dione and thieno[2,3‐d], the two preferred pharmacophores, were rationalized. Assimilation of ‐pyrimidine‐6‐carboxylate hybrids could be advantageous as a lead template for the development of new anti‐diabetic drugs.
A novel series of benzylidene‐thiazolidine‐2,4‐dione linked thieno[2,3‐d]‐pyrimidine‐6‐carboxylate molecules (9 a–o) were synthesized in excellent yields (75–95 %). All the compounds were screened their in vitro antioxidant and anti‐diabetic potentials followed by in silico experiments against human pancreatic α‐amylase and human lysosomal acid α‐glucosidase enzymes, respectively. Among the tested compounds, two compounds were showed potent activity.