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Synthesis and Biological Evaluation of 1,3,5-Trisubstituted 2-Pyrazolines as Novel Cyclooxygenase-2 Inhibitors with Antiproliferative Activity |
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| Authors: | Teymour Vahedpour Jatinder Kaur Salar Hemmati Maryam Hamzeh-Mivehroud Ali Akbar Alizadeh Frank Wuest Siavoush Dastmalchi |
| Affiliation: | 1. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665811 Iran Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, 5165665811 Iran;2. Department of Oncology, University of Alberta, Edmonton, AB, T6G 1Z2 Canada Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H7 Canada;3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665811 Iran;4. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665811 Iran;5. Department of Oncology, University of Alberta, Edmonton, AB, T6G 1Z2 Canada |
| Abstract: | A new series of 1,3,5-trisubstituted 2-pyrazolines for the inhibition of cyclooxygenase-2 (COX-2) were synthesized. The designed structures include a COX-2 pharmacophore SO2CH3 at the para-position of the phenyl ring located at C-5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX-1/COX-2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT-29. The lead compound (4-chlorophenyl){5-[4-(methanesulfonyl)phenyl]-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl}methanone ( 16 ) showed significant COX-2 inhibition (IC50=0.05±0.01 μM), and antiproliferative activity (IC50=5.46±4.71 μM). Molecular docking studies showed that new pyrazoline-based compounds interact via multiple hydrophobic and hydrogen-bond interactions with key binding site residues of the COX-2 enzyme. |
| Keywords: | COX-2 inhibitors 2-pyrazolines anti-inflammatory agents anticancer drugs |