Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR

Eman K A Abdelall; Gehan M Kamel

doi:10.1016/j.ejmech.2016.04.049

Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR

Eur J Med Chem. 2016 Aug 8:118:250-8. doi: 10.1016/j.ejmech.2016.04.049. Epub 2016 Apr 21.

Authors

Eman K A Abdelall¹, Gehan M Kamel²

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 Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt.

PMID: 27131067
DOI: 10.1016/j.ejmech.2016.04.049

Abstract

Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM).

Keywords: 15-Lipoxygenase inhibitors; Anti-inflammatory; Celecoxib analogues; Cyclooxygenase inhibitors; DMFDMA; Ethyl trifloroacetate; SO(2)NH(2) pharmacophores.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / adverse effects
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Arachidonate 15-Lipoxygenase / metabolism*
Cattle
Celecoxib / adverse effects
Celecoxib / chemical synthesis*
Celecoxib / chemistry
Celecoxib / pharmacology*
Chemistry Techniques, Synthetic
Cyclization
Cyclooxygenase 2 / metabolism*
Cyclooxygenase 2 Inhibitors / adverse effects
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology
Lipoxygenase Inhibitors / adverse effects
Lipoxygenase Inhibitors / chemical synthesis
Lipoxygenase Inhibitors / chemistry
Lipoxygenase Inhibitors / pharmacology
Magnetic Resonance Spectroscopy
Male
Pyrazoles / chemistry*
Rats
Stereoisomerism
Thiazoles / chemistry*
Ulcer / chemically induced

Substances

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