Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II

Said A H El-Feky; Zakaria K Abd El-Samii; Nermine A Osman; Jasmine Lashine; Mohamed A Kamel; Hamdy Kh Thabet

doi:10.1016/j.bioorg.2014.12.003

Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II

Bioorg Chem. 2015 Feb:58:104-16. doi: 10.1016/j.bioorg.2014.12.003. Epub 2014 Dec 31.

Authors

Said A H El-Feky¹, Zakaria K Abd El-Samii², Nermine A Osman², Jasmine Lashine², Mohamed A Kamel³, Hamdy Kh Thabet⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, PO Box 840, Rafha 91911, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Electronic address: [email protected].
² Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
³ Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁴ Department of Chemistry, Faculty of Arts and Science, Northern Border University, PO Box 840, Rafha 91911, Saudi Arabia; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11284, Egypt.

PMID: 25590381
DOI: 10.1016/j.bioorg.2014.12.003

Abstract

In continuation of our study of novel quinolines with anti-inflammatory activity using the Pfitzinger reaction, several new quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds (5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a demonstrated the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a were devoid of ulcerogenic activity.

Keywords: Anti-inflammatory; Pyrazoles; Quinoline derivatives; Ulcerogenic activity.

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology*
Cyclooxygenase 2 / chemistry
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology
Molecular Docking Simulation
Proton Magnetic Resonance Spectroscopy
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Pyrazoles / pharmacology*
Quinolines / chemistry*
Rats
Spectrophotometry, Infrared

Substances

Anti-Inflammatory Agents
Cyclooxygenase 2 Inhibitors
Pyrazoles
Quinolines
Cyclooxygenase 2