SYNTHESIS, CHARACTERISATION, IN SILICO MOLECULAR DOCKING STUDIES AND IN VIVO ANTI-INFLAMMATORY ACTIVITY OF SUBSTITUTED 4-THIAZOLIDINONE DERIVATIVES.

Abstract

4-thiazolidinone seems to be a ketone-containing heteroatoms molecule composed of N (nitrogen) and S (sulphur). The goal of the study was to combine the benzimidazole nucleus with thiazolidinone to produce a strong anti-inflammatory effect. The halogenated electron-withdrawing groups on the phenyl ring of 4-thiazolinone generated anti-inflammatory activity. A three-step procedure was used to make eight substituted 4-thiazolidinone (3A-3H) derivatives in this study. Infrared, mass, and nuclear magnetic resonance spectroscopy, as well as elemental analysis techniques were used to interpret the structure of newly synthesized compounds. Further docking based studies were conducted to evaluate the binding affinity of the synthesized compounds towards COX-1 and COX-2 protein targets. By the experimental data it was found that compounds 3D and 3F exhibited higher significant anti-inflammatory activity at 3rd hour being 66.7 and 64.3% respectively, which is more than standard drug indomethacin (61.9%). Compounds 3G and 3E exhibited significant anti-inflammatory activity at 3rd hour 54.3% and 57.1% respectively. The synthesised derivatives had superior affinity with COX-1 and COX-2 channels than that of the recognized anti-inflammatory protein targets. On comparison with the reference compound, which has a binding score of -6.64 kJ/mol for COX-1, synthesised compounds 3E and 3D had the highest docking values of -7.73 kJ/mol for COX-1 and -9.49 kJ/mol for COX-2, respectively. The synthesised derivatives also demonstrate a superior binding profile, with COX-1 and COX-2 protein displaying greater binding energy values, establishing compounds 3A to 3H as effective inhibitors for both the protein targets. Compounds having –OH, –NO2, -F, -OCH3 & -Cl group and thiazolidione nucleus are extra active than the existing compounds.