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

• Published in: Journal of the Iranian Chemical Society Vol. 20; no. 4; pp. 861 - 873
• Main Authors: Jyothi, Mahima, Ranganatha, V. Lakshmi, Khamees, Hussien Ahmed, Khadri, M. J. Nagesh, Khanum, Shaukath Ara
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2023; Springer Nature B.V
• Subjects: Analytical Chemistry; Biochemistry; Chemical synthesis; Chemistry; Chemistry and Materials Science; Denaturation; Inorganic Chemistry; Molecular docking; Morpholine; NMR; Nuclear magnetic resonance; Organic Chemistry; Original Paper; Physical Chemistry; Piperidine; Substitutes; COX-1 and COX-2 activity; benzo[d]thiazole-morpholine benzamides; Anti-inflammatory; benzo[d]thiazole-piperidine benzamides
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-022-02719-0

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, 1 H, 13 C 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 IC 50 (11.34 µM and 11.21 µM) 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.