Design, synthesis, characterization and analysis of anti-inflammatory properties of novel N-(benzo[d]thiazol-2-yl)-2-[phenyl(2-(piperidin-1-yl) ethylamino] benzamides and N-(benzo[d]thiazol-2-yl)-2-[phenyl (2-morpholino) ethylamino] benzamides derivatives through in vitro and in silico approach

A series of novel N-(benzo[d]thiazol-2-yl)-2-[phenyl(2-(piperidin-1-yl) ethylamino] benzamides 8(a-e) and N-(benzo[d]thiazol-2-yl)-2-[phenyl(2-morpholino) ethylamino] benzamides 9(a-e) derivatives were synthesized in good yield by coupling substituted 2-amino benzothiazoles 3(a-e) with N-phenyl anthranilic acid 4. Further, the obtained intermediate compounds substituted N-(Benzo[d]thiazol-2-yl)-2-(phenylamino) benzamides 5(a-e) was treated with 1-(2-chloro ethyl) piperidine hydrochloride 6 to yield the final derivatives 8(a-e) and with 4-(2-chloro ethyl) morpholine hydrochloride 7 to yield 9(a-e) derivatives. The purity of the synthesized compounds was judged by their C, H and N analysis and the structure was analyzed based on IR, H-1, C-13 NMR and mass spectral data. The compounds 8(a-e) and 9(a-e) were evaluated for anti-inflammatory activity and among the series, compounds 8b and 9b with a methoxy group at the sixth position in the benzothiazole ring appended with piperidine and morpholine moieties, respectively, showed the highest IC50 (11.34 mu M and 11.21 mu M) values for COX-1 inhibition, whereas the same compounds 8b and 9b demonstrated excellent COX-2 SI values (SI = 103.09 and 101.90, respectively) and even showed 78.28% and 69.64% inhibition of albumin denaturation. Further, molecular docking studies have been accomplished and supported for the potent compound to check the three-dimensional geometrical view of the ligand binding to their protein receptor.

Automated summary

A series of novel N-(benzo[d]thiazol-2-yl)-2-[phenyl(2-(piperidin-1-yl) ethylamino] benzamides and N-(benzo[d]thiazol-2-yl)-2-[phenyl(2-morpholino) ethylamino] benzamides derivatives were successfully synthesized and evaluated for their anti-inflammatory activity. Compounds with a methoxy group at the sixth position in the benzothiazole ring appended with piperidine and morpholine moieties showed the highest COX-1 inhibition and excellent COX-2 selectivity.