Affiliation:
1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey
2. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey
Abstract
Considerable efforts have been directed towards the discovery of selective cyclooxygenase isoxyme 1 (COX-1) inhibitors due to the recent work highlighting the involvement of COX-1 in the pathogenesis of pain, neuroinflammation, cancer and cardiovascular disorders. In this context, this paper aims to describe 2-pyrazolines endowed with selective COX-1 inhibitory potency. An efficient microwave-assisted synthetic method was applied for the preparation of a series of pyrazolines, which were tested for their COX-1 and cyclooxygenase isoxyme 2 (COX-2) inhibitory effects using a colorimetric assay. The cytotoxic properties of the most potent derivatives on NIH/3T3 fibroblast cells were determined using MTT method. 1-(3-Fluorophenyl)-5-(3,4-methylendioxyphenyl)- 3-(2-thienyl)-4,5-dihydro-1H-pyrazole (2g) and 1-(3-bromophenyl)- 5-(3,4-methylendioxyphenyl)-3-(2-thienyl)-4,5-dihydro-1H-pyrazole (2h) were determined as selective COX-1 inhibitors. According to the in silico data obtained from Schr?dinger?s QikProp module, both compounds are estimated to possess favourable oral bioavailability and drug-likeness. This work could be a rational guideline for further modifications at different sites on 2-pyrazoline motif to bring out a new class of selective COX-1 inhibitors.
Publisher
National Library of Serbia
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