Cyclooxygenase-2 and 15-lipoxygenase inhibition, synthesis, anti-inflammatory activity and ulcer liability of new celecoxib analogues: Determination of region-specific pyrazole ring formation by NOESY

Eman K A Abdelall; Phoebe F Lamie; Waleed A M Ali

doi:10.1016/j.bmcl.2016.04.046

Cyclooxygenase-2 and 15-lipoxygenase inhibition, synthesis, anti-inflammatory activity and ulcer liability of new celecoxib analogues: Determination of region-specific pyrazole ring formation by NOESY

Bioorg Med Chem Lett. 2016 Jun 15;26(12):2893-2899. doi: 10.1016/j.bmcl.2016.04.046. Epub 2016 Apr 19.

Authors

Eman K A Abdelall¹, Phoebe F Lamie², Waleed A M Ali³

Affiliations

¹ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: eman.ahmed@pharm.bsu.edu.eg.
² Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
³ Department of Biochemistry, Cairo General Hospital, Cairo, Egypt.

PMID: 27158139
DOI: 10.1016/j.bmcl.2016.04.046

Abstract

Two new series of 1,5-diaryl pyrazoline (3a-f) and 1,5-diaryl pyrazole (5a and 5b) were designed as both COX-2 and 15-LOX inhibitors. All the prepared compounds were fully characterized by all spectral and element analysis. Their anti-inflammatory activity and ulcer index were included. Pyrazoline 3f is the most effective with IC50=1.14 and 4.7μM against COX-2 and 15-LOX respectively, and more potent than celecoxib and meclofenamate references. In addition 3a, 3b, 5a, and 5b were safer with low ulcer index than celecoxib. Docking study was performed for the most active compounds such as 2b, 3a, and 3f on COX-2 and 15-LOX enzymes.

Keywords: 15-Lipoxygenase inhibitors; Antiinflammatory; Cyclooxygenase inhibitors; Diethyl oxalate; Sulfonamide pharmacophores.

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Arachidonate 15-Lipoxygenase / metabolism
Celecoxib / chemical synthesis
Celecoxib / chemistry
Celecoxib / pharmacology*
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Humans
Lipoxygenase Inhibitors / chemical synthesis
Lipoxygenase Inhibitors / chemistry
Lipoxygenase Inhibitors / pharmacology*
Models, Molecular
Molecular Structure
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Lipoxygenase Inhibitors
Pyrazoles
Arachidonate 15-Lipoxygenase
Cyclooxygenase 2
Celecoxib