72344-14-0Relevant academic research and scientific papers
Synthesis and Biological Evaluation of 1,3,5-Trisubstituted 2-Pyrazolines as Novel Cyclooxygenase-2 Inhibitors with Antiproliferative Activity
Vahedpour, Teymour,Kaur, Jatinder,Hemmati, Salar,Hamzeh-Mivehroud, Maryam,Alizadeh, Ali Akbar,Wuest, Frank,Dastmalchi, Siavoush
, (2021/02/27)
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.
Design, synthesis and biological evaluation of new 1,3-diphenyl-3-(Phenylamino)propan-1-ones as selective cyclooxygenase (COX-2) inhibitors
Farzaneh, Shabnam,Shahhosseini, Soraya,Arefi, Hadi,Esfahanizadeh, Marjan,Zarghi, Afshin,Daraei, Bahram
, p. 652 - 659 (2018/11/21)
Background: Prostaglandins are a family of eicosanoids biosynthesized from arachi-donic acid through cyclooxygenase (COX) pathway. Two isoforms of COX are well established: COX-1, COX-2. Evidence supports the notion that cyclooxygenase-2, plays a crucial role in some pathological conditions such as inflammation and cancer. Objective: A new group of 1,3-diphenyl-3-(phenylamino)propan-1-ones was designed and synthesized to investigate for their COX-2 inhibitory activity and inhibition of platelet aggregation. Method: Docking study was performed using AutoDock vina software. In vitro COX-1 and COX-2 isozyme inhibition studies were accomplished to obtain structure activity relationship data. The in vitro antiplatelet aggregation activity was determined by turbidimetric procedure. Results: In vitro COX inhibition assay showed that except compound 8c, all derivatives were selective COX-2 inhibitors with IC50 values in the potent 0.20-0.35 μM range with high COX-2 selectivity indexes (SI). Molecular modeling and docking studies indicated that synthesized compounds had a binding similar to that of the known inhibitor SC-558 and the SO2 Me group was inserted into the COX-2 secondary pocket (Val523, Phe518, Ile517, Arg513 and His90) and C=O of the central α, β-unsaturated-carbonyl moiety was oriented toward the entrance to the COX-2 binding site (Tyr355 and Arg120). Conclusion: The 1,3-diphenyl-3-(phenylamino)propan-1-ones are novel COX-2 inhibitors with good COX-2 inhibitory and low affinity for COX-1 isoenzyme. Also our results demonstrated that majority of these compounds inhibited AA-induced platelet aggregation.
Novel 1,3,5-triphenyl-2-pyrazolines as anti-infective agents
Sivakumar,Prabhu Seenivasan,Kumar, Vanaja,Doble, Mukesh
scheme or table, p. 3169 - 3172 (2010/07/20)
Sixteen 1,3,5-triphenyl-2-pyrazolines were synthesized and their anti-infective activities (against Mycobacterium tuberculosis H37Rv, six bacterial and four fungal strains) were tested. Only compound with SO2CH3 in the para position of the A-ring was active against the tubercular strain at 100 μg/ml concentration. All compounds showed good anti infective activity against Escherichia coli and poor activity against Staphylococcus aureus. Compounds 4, 12, 13 and 14 exhibited reasonable activity against all the organisms tested (88% reduction) against four fungi studied at 2 mg/ml. All these compounds possess halogen substitutions. Compound 11 showed very high activity (>90%) against three fungi. Majority of the compounds showed more than 90% inhibition against one or two fungi. Since pyrazolines are reported to inhibit the activity of p-glycoprotein, they may prevent drug resistance developed by microorganism.
