Synthesis, Characterization and In-vitro Anti-Inflammatory Activity of Methoxydibenzofuran -1,3-Thiazole-Carboxamide Derivatives.

Abstract

The dibenzofuranthiazole group encompasses a well-established array of molecules that have yielded pharmacologically and biologically active agents with diverse heterocyclic and linear structures. Despite the potency of existing drugs like Tetomilast, Oglemilast, and Ciliomilast as anti-inflammatory agents, they are associated with significant side effects such as nausea, vomiting, and gastric acid secretion. Moreover, many contemporary standard drugs exhibit undesirable effects, including drug resistance, highlighting the urgent need for newer agents with improved potency and fewer adverse reactions. This study aimed to explore a set of new compounds synthesized through a four-step procedure involving coupling reactions. The purity of all synthesized derivatives was verified primarily through melting point, thin-layer chromatography, and FTIR spectroscopy, complemented by 1HNMR and Mass spectra studies. Additionally, the anti-inflammatory activities of the synthesized compounds were assessed using the protein denaturation assay method. The yields of all synthesized compounds ranged from 54% to 87%, demonstrating a moderate inhibition effect. Notably, compounds 4c, 4d, 4e, 4f, 4g, and 4h exhibited promising activity compared to the standard drug diclofenac sodium at a low concentration (100 µg/ml), with inhibition percentages ranging from 26.70% to 38.54%, surpassing diclofenac sodium's inhibition rate of 25.31 µg/ml. Particularly, compound 4d demonstrated significant inhibitory properties across all concentrations tested. This experiment suggests that the anti-inflammatory activity of dibenzofuranthiazole carboxamide derivatives is primarily attributed to halogenic derivatives with para substitution. Fluoro and chloro substitutions were identified as key enhancers of activity, along with methoxy derivatives bearing meta substituents exhibiting moderate activity.