Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and <i>in vivo</i> studies

<p>Twelve new derivatives of benzothiazole bearing benzenesulphonamide and carboxamide were synthesised and investigated for their <i>in vivo</i> anti-inflammatory, analgesic and ulcerogenic activities. Molecular docking showed an excellent binding interaction of the synthesised compounds with the receptors, with <b>17c</b> showing the highest binding energy (–12.50 kcal/mol). Compounds <b>17c</b> and <b>17i</b> inhibited carrageenan-induced rat paw oedema at 72, 76, and 80% and 64, 73, and 78% at 1 h, 2 h, and 3 h, respectively. In the analgesic activity experiment, compounds <b>17c</b>, <b>17 g</b>, and <b>17i</b> had ED<sub>50</sub> (µM/kg) of 96, 127, and 84 after 0.5 h; 102, 134, and 72 after 1 h and 89, 156, and 69 µM/kg after 2 h, respectively, which were comparable with 156, 72, and 70 µM/kg for celecoxib. The ulcerogenic index of the most active derivatives <b>17c</b> and <b>17i</b> were 0.82 and 0.89, respectively, comparable to 0.92 for celecoxib. The physicochemical studies of the new derivatives showed that they will not have oral bioavailability problems.</p>