252006-56-7Relevant academic research and scientific papers
Amine-functionalized nano-NaY zeolite for the synthesis of N-acetyl pyrazoles and dihydropyrimidines
Razavian Mofrad, Raheleh,Kabirifard, Hassan,Tajbakhsh, Mahmood,Firouzzadeh Pasha, Ghasem
, (2021/08/23)
An efficient base-catalyzed synthesis of dihydropyrimidines and N-acetyl pyrazoles is reported using 1-(2-aminoethyl)piperazine-modified nano-NaY zeolite (ZeSi–AP) under mild and green conditions. The structure of the catalyst was identified by using FT-IR, XRD, TGA, DTA, DLS, SEM, TEM, and elemental analyses. This heterogeneous catalyst has many benefits, such as a simple work-up procedure, high product yield, and it is easily regenerated and reused at least for four cycles without losing its activity.
Structure-activity relationship with pyrazoline-based aromatic sulfamates as carbonic anhydrase isoforms I, II, IX and XII inhibitors: Synthesis and biological evaluation
Moi, Davide,Nocentini, Alessio,Deplano, Alessandro,Balboni, Gianfranco,Supuran, Claudiu T.,Onnis, Valentina
, (2019/08/30)
Four new series of aromatic sulfamates were synthesized and investigated for the inhibition of four human (h) isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I, II, IX, and XII. The reported derivatives, obtained by a sulfamoylation reaction of the corresponding phenolic precursors, bear 3,5-diarylpyrazoline moieties as spacers between the benzenesulfamate fragment which binds the zinc ion from the active site, and the tail of the inhibitor. Pyrazolines are biologically privileged scaffolds, endowed with versatile biological activity, such as an anti-proliferative action. The derivatives were tested for the inhibition of the cytosolic, hCA I and II (off target isoforms) and the trans-membrane, tumor-associated hCA IX and XII enzymes (anticancer drug targets). Generally, hCA I was not effectively inhibited, whereas many low nanomolar inhibitors were evidenced against hCA II (KIs in the range of 0.42–90.1 nM), IX (KIs in the range of 0.72–63.6 nM), and XII (KIs in the range of 0.88–85.2 nM). The best substitution fragments at the pyrazoline ring included for CA II a 4-sulfamic group on the 3-aryl and halogens on the 5-aryl or a methoxy group on the 3-aryl and a 4-sulfamate group on the 5-aryl; for CA IX and CA XII they included the sulfamic group on the 3- or 4-position of the 5-aryl and an electronwithdrawing group on the 4-postion of the 3-aryl ring.
Synthesis, biological evaluation, and molecular docking study of some new pyrazoline derivatives as cyclooxygenase-II inhibitors and anti-inflammatory agents
Bhadoriya, Upendra,Jain, Dinesh K.
, p. 407 - 413 (2018/09/25)
New pyrazoline derivatives bearing chalcone frame were synthesized, characterized, and evaluated for their cyclooxygenase-II (COX-II) inhibitory activity and anti-inflammatory potential. The synthesis of intermediate chalcone derivative was carried out through Claisen-Schmidt reaction between carbonyl compounds while cyclization of chalcone by acetylated hydrazine hydrate offered diaryl pyrazoline moiety. The incorporation of α-β unsaturated keto group (chalcone frame) was achieved through base catalyzed condensation reaction between carbonyl group of N-acetyl pyrazoline and aryl aldehyde. The compound (E)-3-(4-hydroxyphenyl)-1-(3-(4-hydroxyphenyl)-5-phenyl-4,5-dihydropyrazol-1-yl)prop-2-en-1-one (6i) exhibited potent COX-II inhibitory activity. The inhibition of COX-II enzyme was found to be 85.3% for compound 6i and 70.4% for reference standard celecoxib. The carrageenan-induced rat paw edema method was employed to determine in vivo anti-inflammatory potential and 42.41% of inhibition in diameter of rat paw edema was measured for compound 6i. Moreover, molecular docking study was also performed using “Maestro (Schr?dinger) Molecular Docking Software,” and the results of docking study revealed prompt binding interactions between synthesized compound and target receptor. The compound which was found to be most potent one in biological study also exhibited good docking potential in molecular docking study, and hydrogen bond was observed between potent compound 6i and amino acid residue of target protein receptor.
Design, Synthesis, and Biological Evaluation of Pyrazoline-Based Hydroxamic Acid Derivatives as Aminopeptidase N (APN) Inhibitors
Cao, Jiangying,Zang, Jie,Ma, Chunhua,Li, Xiaoguang,Hou, Jinning,Li, Jin,Huang, Yongxue,Xu, Wenfang,Wang, Binghe,Zhang, Yingjie
supporting information, p. 431 - 436 (2018/02/21)
Aminopeptidase N (APN) has been recognized as a target for anticancer treatment due to its overexpression on diverse malignant tumor cells and association with cancer invasion, metastasis and angiogenesis. Herein we describe the synthesis, biological evaluation, and structure–activity relationship study of two new series of pyrazoline analogues as APN inhibitors. Among these compounds, 5-(2-(2-(hydroxyamino)-2-oxoethoxy)phenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (compound 13 e) showed the best APN inhibition with an IC50 value of 0.16±0.02 μm, which is more than one order of magnitude lower than that of bestatin (IC50=9.4±0.5 μm). Moreover, compound 13 e was found to inhibit the proliferation of diverse carcinoma cells and to show potent anti-angiogenesis activity. At the same concentration, compound 13 e presents significantly higher anti-angiogenesis activity than bestatin in human umbilical vein endothelial cells (HUVECs) capillary tube formation assays. The putative binding mode of 13 e in the active site of APN is also discussed.
Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin
Luan, Shenglin,Zhong, Hang,Zhao, Xuan,Yang, Jinyu,Jing, Yongkui,Liu, Dan,Zhao, Linxiang
supporting information, p. 584 - 595 (2017/11/14)
Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycin-resistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI50 = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer.
Synthesis and cytotoxicity studies of 3,5-diaryl N-acetyl pyrazoline - Isatin hybrids
Sharma, Manmohan,Sharma, Sahil,Buddhiraja, Abhishek,Saxena,Nepali, Kunal,Bedi
, p. 4337 - 4344 (2015/04/22)
Numerous reports highlighting the cytotoxic effects of 3,5-diaryl N-acetyl-pyrazolines and isatin tempted us to synthesise conjugates of the functionalities via alkyl armed triazole tetheration. The hybrids were synthesized by click chemistry approach and were evaluated against a panel of cell lines i.e. viz HeLa (cervix cancer), CAKI-I (Renal cancer), PC-3 (Prostate cancer) and Mia-paca-2 (pancreatic cancer). The hybrids were classified into right-handed and left-handed conjugates on the basis of the placement of the isatin ring. The length of the alkyl armed triazole linker was varied from 2 to 6. Structure activity relationship has also been presented. A preliminary cytotoxic assay was performed on the series of 3,5-diaryl N-acetyl-pyrazolines and only the potent 3,5-diaryl N-acetylpyrazolines were selected for their inclusion in the hybrid scaffold. Among the cell lines employed, HeLa cell line was the most sensitive towards the exposure of test compounds. Out of all the compounds evaluated, two right-handed conjugates MI-7b and MI-8b and two left-handed conjugates MI-4b, MI-6b displayed significant cytotoxic potential and exhibited an IC50 range from 1.3 to 3.5 μM against HeLa Cell line.
Synthesis of 1,2,3-triazole tethered bifunctional hybrids by click chemistry and their cytotoxic studies
Singh, Jagjeet,Sharma, Sahil,Saxena,Nepali, Kunal,Bedi, Preet Mohinder Singh
, p. 3160 - 3169 (2013/07/11)
In view of the drug resistance with most of the currently used anticancer drugs, molecular hybrids of pyrazolyl chalcones and p-nitro benzyl functionalities tethered by triazole ring have been synthesised and evaluated for cytotoxic studies against three human cancer cell lines (THP, COLO-205, A-549). The results of the preliminary investigation exhibited marked dependence of the cytotoxic activity on the electronic factors. Placement of naphthyl (JGPT-11) and trimethoxy phenyl ring (JGPT-6) as ring A proved to be extremely beneficial in enhancing the cytotoxic potential. Thus we herein report the synthesis and cytotoxic studies of a new class of molecular hybrids. Detailed investigation on the biological mechanistic insights of JGPT-11 and 6 is under progress.
Synthesis of some pyrazole derivatives and preliminary investigation of their affinity binding to P-glycoprotein
Manna, Fedele,Chimenti, Franco,Fioravanti, Rossella,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Ferlini, Cristiano,Scambia, Giovanni
, p. 4632 - 4635 (2007/10/03)
A series of substituted pyrazolines were synthesized and evaluated for their anticancer activity and for their ability to inhibit P-glycoprotein- mediated multidrug resistance by direct binding to a purified protein domain containing an ATP-binding site and a modulator interacting region. Compounds 2a and e have been found to bind to P-glycoprotein with greater affinity.
Difunctional Heterocycles: A Convenient Synthesis of Bis(4,5-dihydropyrazolyl) ethers from Their Precursors Bis(chalcones)
Elwahy, Ahmed H. M.
, p. 2582 - 2596 (2007/10/03)
The new bis(4,5-dihydropyrazolyl)ethers 18-22, 26, 27 and 40-44 were prepared in 30-80 percent yields by condensation of the corresponding bis(chalcones) 13-17 and 34-37 with each of hydrazine and phenylhydrazine. Attemptes to prepare compound 20 by alkylation of 24 with 1,4-dibromobutane were unsuccessful and instead the monoalkylated derivatives 25 was obtained in 45 percent yield. Compound 24 was obtained in 63 percent yield by reacting 23 with hydrazine hydrate in refluxing acetic acid. The bis(chalcones) 13-17 and 34-37 were obtained in 65-80 percent yields by basic condensation of each of the bis(acetyl) derivatives 8-12 and the bis(aldehyde) derivatives 30-33 with benzaldehyde and acetophenone respectively. Compounds 14, 15, 35 and 36 were alternatively obtained in 32-44 percent yields by alkylation of each of the 4-cinnamoylphenol 23 and 4-benzoylvinylphenol 38 with the appropriate dibromoalkane.
