COX-1/COX-2 inhibition assays and histopathological study of the new designed anti-inflammatory agent with a pyrazolopyrimidine core

Eman K A Abdelall; Phoebe F Lamie; Amira K M Ahmed; El-Shaymaa El-Nahass

doi:10.1016/j.bioorg.2019.01.031

COX-1/COX-2 inhibition assays and histopathological study of the new designed anti-inflammatory agent with a pyrazolopyrimidine core

Bioorg Chem. 2019 May:86:235-253. doi: 10.1016/j.bioorg.2019.01.031. Epub 2019 Jan 22.

Authors

Eman K A Abdelall¹, Phoebe F Lamie², Amira K M Ahmed², El-Shaymaa El-Nahass³

Affiliations

¹ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: [email protected].
² Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
³ Department of Pathology, Faculty of Veterinary Medicine, Beni-suef University, 62511, Egypt.

PMID: 30716621
DOI: 10.1016/j.bioorg.2019.01.031

Abstract

Four pyrazolopyrimidine series were prepared with a substitution at position- 4 by Schiff base, triazole, oxadiazole and pyrazole moieties (7a-f, 8a,b, 9a-f, 10a,b and 13a,b), respectively. All the synthesized compounds were evaluated in vitro against COX-2 and in vivo against carrageenan-induced rat paw edema as anti-inflammatory agents. Regarding the anti-inflammatory activity (AI) compounds 7c, 7f, 8a, and 9a showed higher activity with respect to celecoxib. Compounds 9a, 7d, and 7f were closely selective to celecoxib. Also, 7c and 7d were safer than indomethacin and similar to celecoxib as resulted from the histopathological study. In addition, the docking study that showed the binding mode of prominent pyrazolopyrimidine compounds inside the COX-2 receptor. Formation of unexpected pyrazole 13a and 13b was briefly discussed using 2D NMR.

Keywords: Anti-inflammatory; COX-2 inhibitors; Celecoxib; Pyrazolo[3,4-d] pyrimidine; SO(2)Me pharamacophores.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Carrageenan / administration & dosage
Cattle
Cyclooxygenase 1 / metabolism*
Cyclooxygenase 2 / metabolism*
Cyclooxygenase Inhibitors / chemical synthesis
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Drug Design
Edema / chemically induced
Edema / drug therapy*
Edema / pathology
Injections, Subcutaneous
Molecular Docking Simulation
Molecular Structure
Pyrazoles / chemical synthesis
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Rats
Rats, Wistar
Stomach / drug effects
Stomach / pathology
Structure-Activity Relationship
Ulcer / drug therapy
Ulcer / pathology

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase Inhibitors
Pyrazoles
Pyrimidines
pyrazolylpyrimidine
Carrageenan
Cyclooxygenase 1
Cyclooxygenase 2