New 2-aminobenzothiazole derivatives: Design, synthesis, anti-inflammatory and ulcerogenicity evaluation

New 2-aminobenzothiazole derivatives: Design, synthesis, anti-inflammatory and ulcerogenicity evaluation

•Novel twenty benzothiazole amides were designed as anti-inflammatory agents.•Compounds 3h, 6a were the most potent with comparable activities to indomethacin.•Compound 6a revealed the best GI tolerability.•Compound 6a exerted its anti-inflammatory activity through COX-2 inhibition.•Molecular dockin...

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Bibliographic Details
Published in:Journal of molecular structure Vol. 1291; p. 136042
Main Authors: Awaad, Sara S., Sarhan, Mona O., Mahmoud, Walaa R., Nasr, Tamer, George, Riham F., Georgey, Hanan H.
Format: Journal Article
Language:English
Published: Elsevier B.V 05-11-2023
Subjects:
Anti-inflammatory
Benzothiazole
Carrageenan induced paw edema
COX inhibitors
Carrageenan induced paw edema
Anti-inflammatory
Benzothiazole
COX inhibitors
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Summary:•Novel twenty benzothiazole amides were designed as anti-inflammatory agents.•Compounds 3h, 6a were the most potent with comparable activities to indomethacin.•Compound 6a revealed the best GI tolerability.•Compound 6a exerted its anti-inflammatory activity through COX-2 inhibition.•Molecular docking confirmed the work hypothesis. Two series of twenty diversely substituted benzothiazole amides were designed and synthesized aiming to obtain derivatives with potential anti-inflammatory activity and decreased GIT ulceroginicity. All the synthesized compounds were in-vivo screened for their anti-inflammatory activity using carrageenan induced rat hind paw edema model. Results revealed that compounds 3h and 6a were the most potent ones with remarkable GIT tolerability compared to indomethacin (ED50 = 0.012, 0.016 and 0.015 mmol/kg, respectively). Moreover, compounds 3h and 6a ulcerogenic investigation proved ulcer index= 0 at the first 2 doses (0.01, 0.02 mmol/kg) and surpassing the third dose (0.03 mmol/kg) for 6a only, respectively. In vitro COX-1/COX-2 isozyme selectivity testing revealed the best selectivity index for compound 6a (SI= 3.10) among the investigated compounds compared to celecoxib (SI= 11.89), which was further confirmed with the molecular docking study. [Display omitted]
ISSN:0022-2860
1872-8014
DOI:10.1016/j.molstruc.2023.136042