“DESIGN, SYNTHESIS, CHARACTERIZATION, AND ANTI-COAGULANT ACTIVITY OF SOME NOVEL THIAZOLIDINE-2, 4-DIONE MOLECULES”

Background: Thiazolidine-2,4-dione (TZD) derivatives have gained significant attention in medicinal chemistry due to their diverse pharmacological activities.While their antidiabetic and anti-inflammatory properties are well established, their potential as anti-coagulant agents remains underexplored.This study aims to design, synthesize, and evaluate the anti-coagulant activity of novel thiazolidine-2,4-dione derivatives, which may offer an alternative to existing anticoagulant drugs.Objective: The primary objective of this research is to design, synthesize, and characterize novel thiazolidine-2,4-dione derivatives and evaluate their potential as anti-coagulant agents using in-vitro and in-silico approaches. Methods:The design of thiazolidine-2,4-dione derivatives was guided by molecular docking studies targeting essential coagulation factors, including thrombin (Factor IIa) and Factor Xa.A series of novel derivatives were synthesized through a multi-step reaction sequence involving condensation, cyclization, and purification steps.The synthesized molecules were characterized using Fourier Transform Infrared (FTIR) spectroscopy, Nuclear Magnetic Resonance (NMR) spectroscopy, Liquid Chromatography-Mass Spectrometry (LC-MS), and Elemental Analysis to confirm their chemical structures.The anti-coagulant activity of the derivatives was evaluated using in-vitro assays, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT).Molecular docking was performed to investigate binding interactions with thrombin and Factor Xa.Results: A total of 3 novel thiazolidine-2,4-dione derivatives were successfully synthesized with excellent yields and purity.Spectroscopic characterization confirmed the molecular structure and integrity of the synthesized derivatives.Molecular docking studies revealed that several derivatives exhibited strong binding affinity with thrombin and Factor Xa, with key interactions observed at critical amino acid residues.The invitro anti-coagulant activity tests demonstrated significant prolongation of aPTT, PT, and TT, indicating anticoagulant potential.Among the synthesized derivatives, compound 3 displayed the most potent anticoagulant activity, with results comparable to standard anticoagulant drugs.Structure-activity relationship (SAR) analysis revealed that the presence of electron-donating and electron-withdrawing substituents at specific positions on the TZD core significantly influenced anticoagulant potency. Conclusion:This study successfully designed, synthesized, and characterized novel thiazolidine-2,4-dione derivatives with promising anticoagulant activity.The results indicate that these derivatives have the potential to act as direct thrombin and Factor Xa inhibitors.The study provides a foundation for further optimization and preclinical evaluation of thiazolidine-2,4-dione derivatives as anticoagulant agents.