Design, synthesis, biological evaluation, and computational studies of novel thiazolo-pyrazole hybrids as promising selective COX-2 inhibitors: Implementation of apoptotic genes expression for ulcerogenic liability assessment.

Autor: Marzouk AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt., Taher ES; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt. Electronic address: ehabtaher@azhar.edu.eg., Shaykoon MSA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt., Lan P; Institute for Advanced and Applied Chemical Synthesis, Jinan University, Guangzhou 510632, China., Abd-Allah WH; Pharmaceutical Chemistry Department, Collage of Pharmaceutical Science and Drug Manufacturing, Misr University for Science and Technology, P.O. 77, 6th of October City, Giza, Egypt., Aboregela AM; Basic Medical Science, College of Medicine, University of Bisha, Saudi Arabia; Human Anatomy and Embryology, faculty of medicine, Zagazig University, Zagazig, Egypt., El-Behairy MF; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufiya 32897 Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2021 Jun; Vol. 111, pp. 104883. Date of Electronic Publication: 2021 Mar 31.
DOI: 10.1016/j.bioorg.2021.104883
Abstrakt: A novel series of thiazolo-pyrazole hybrids has been prepared and assessed for their in vitro COX-1/COX-2 inhibitory activity. Compound 6c exhibited the most selective COX-2 inhibition profile (SI of 264) not far of Celecoxib (294). In-vivo anti-inflammatory activity revealed that compound 6d exhibited the highest activity (97.30% inhibition of edema) exceeding reference standard Indomethacin (84.62% inhibition of edema). The ulcerogenic liability tested, using gross, microscopic, biochemical analysis and apoptotic genes expression, showed that compound 6b matched the optimal candidate activity (ulcer index = 120, selectivity index of ~ 162 and 77% in-vivo inhibition of edema). Meanwhile, compound 6 m (ulcer index = 0) showcased the highest safety profile. Molecular modeling analysis and drug likeness studies presented appreciated agreement with the biological evaluation.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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