New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Abstract

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.

Evaluation of Antimicrobial and Chemopreventive Properties and Phytochemical Analysis of Solanum nigrum L. Aerial Parts and Root Extracts

“…DCF was measured using a Varioscan LUX microplate reader at λex = 485 nm and λem = 535 nm. Results were presented as E/E 0 , where E is the value of the test sample and E0 is the control value [62,63].…”

A Review on Oxadiazoles as a Pharmacologically Active Nucleus

“…Two of the synthesized derivatives showed better activity both in vitro as well as in vivo at MIC=40.00-80.00µg/ml as compared to the reference acarbose (MIC=34.72µg/ml) (32a-32b). Teresa Glomb et al [36] innovated new oxadiazole analogues of pyridothiazine-1,1dioxide. Few of the synthesized compounds exhibited COX inhibition at a minimum inhibitory concentration of 100µM (either COX-1 or COX-2) while others displayed no inhibitory activity compared to the reference Meloxicam (40a-40d).…”

In Vitro and In Silico Evaluation of New 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone as Promising Cyclooxygenase Inhibitors

“…The binding mode of inhibitors was correctly predicted when its RMSD was found to be less than 1 Å. The protein and ligand preparation and docking procedure were described in detail in previous studies [48][49][50]. Lamarckian genetic algorithm with local search was employed with a total of 200 runs for each binding site.…”