3-Carboxy-pyrazolinalanine as a new scaffold for developing potent and selective NMDA receptor antagonists

Tamborini, Lucia; Pinto, Andrea; Mastronardi, Federica; Iannuzzi, Maria C.; Cullia, Gregorio; Nielsen, Birgitte; Micheli, Carlo De; Conti, Paola

doi:10.1016/j.ejmech.2013.07.010

Cited by 13 publications

(4 citation statements)

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“…[18] The heterocycles compris-ing an amino acid moiety have recently shown to be very useful tools in medicinal chemistry studies. [19] Therefore, a new synthetic route towards the formation of such compounds is of great interest. From the literature amino acids and some of their derivatives were also found to have antioxidant activity.…”

Section: Introductionmentioning

confidence: 99%

“…3‐carboxy pyrazole α‐amino acid compound identified as antagonist of the N ‐methyl‐d‐aspartic acid (NMDA) receptor showed antitumor activity, as well [18] . The heterocycles comprising an amino acid moiety have recently shown to be very useful tools in medicinal chemistry studies [19] . Therefore, a new synthetic route towards the formation of such compounds is of great interest.…”

Section: Introductionmentioning

confidence: 99%

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Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

et al. 2023

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Pancreatic lipase (PL) inhibitors have received considerable attention by several researchers because of its ability to hydrolyse the triglycerides in the small intestine. This study reports the (i) synthesize of new pyrazole derivatives binding amino acid and Dicyclohexylurea (DCU), (ii) their pharmaceutical potentials-via enzyme inhibitory activity towards PL and antioxidant activities (using complementary antioxidant methods including FCR, FRAP and ORAC), (iii) the possible interactions between pyrazole compounds and PL enzyme through in silico studies, and the pharmacokinetic properties of the tetra-substituted pyrazole analogues by PreADMET. Enzyme activities with IC 50 values of the pyrazole analogues were found to be in a high range of 6.6 � 0.4 μM to 13.5 � 0.2 μM. However, antioxidant activities of the pyrazole analogues exhibited low binding affinities against FCR, FRAP, and ORAC. The pyrazole analogues with docking scores were in the range of À 7.3 to À 15.2 and their SAR analysis were demonstrated to highlight the importance of amino acid and DCU linked scaffolds. Two web tools were utilized for the purpose of predicting ADMET parameters of drugs and drug-like pyrazole analogues. These results suggested that the amino acid and DCU linked pyrazole analogues have potential as PL inhibitors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

et al. 2023

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“…It was reported that maximally treatments are with nitrogen containing chemical entity only. Studies revealed that pyrazoline derivatives possess therapeutic potential like antimicrobial (Siddiqui et al, 2011;Turan-Zitouni et al, 2007), analgesic (Samshuddin et al, 2012;James and Bhat, 2012), anti-in lammatory (Sharma et al, 2012), antiameobic (Wani et al, 2012), antitubercular (Taj et al, 2011), antimalarial (Acharya et al, 2010), anticonvulsant, antidepressant (Özdemir et al, 2007;Palaska, 2001), antioxidant (Isloor et al, 2013), antiparkinsonism (Amr et al, 2008), antileishmanial (Rizvi et al, 2012), antihyperglyceamic (Ovais et al, 2013), hepatoprotective (Khalilullah et al, 2011), angiotensin converting enzyme inhibitor (Bonesi et al, 2010), MOA inhibitors (Mathew et al, 2014), B-Raf kinase inhibitor (Jeong et al, 2004), β-Ketoacyl-acyl carrier protein synthase III inhibitor (Blackburn et al, 2010), EGFR kinase inhibitor (Duffey et al, 2010), GluN2C/GluN2D selective antagonist (Qin et al, 2015), 5-Hydroxytryptamine 6 receptor antagonist (Acker et al, 2013), NMDA receptor antagonist (Loevezijn et al, 2011), Cannabinoid receptor antagonist (Tamborini et al, 2013) and anticancer activity (Bashir et al, 2011;Hayat et al, 2010;Wang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, molecular docking and in vitro anticancer activity of 3-(4-methoxyphenyl)-5-substituted phenyl-2-pyrazoline-1- carbothioamide

Sahu

Rajapandi

Maji

et al. 2021

ijrps

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In the present study, eight numbers of new 3- (4-methoxy phenyl)-5-substituted phenyl-2-pyrazoline-1-carbothioamide (5a-h) have been synthesized from 1- (4-methoxy phenyl)-3- (substituted phenyl)-prop-2-en-1-one (3a-h) and structurally characterized by using FT-IR, 1H NMR, 13C NMR, Mass and Elemental analysis. The synthesized molecules were biologically evaluated for their in vitro anticancer activity against human breast adenocarcinoma (MCF-7), liver cancer (Hep-G2) and leukaemia cancer (K-562) cell line using Sulforhodamine B (SRB) bioassay technique. From the all synthesized compounds 5a, 5c, 5d, and 5e exhibited potent anticancer activity (GI50= <10µg/ml) as compared to the controlled drug 5-Fluorouracil (5-FU) (GI50=44.5µg/ml) and Adriamycin (ADR) (GI50= <10µg/ml) on MCF-7 cell lines. Besides this, all the synthesized compounds have exhibited moderate activity against human liver cancer (Hep-G2) and leukaemia cancer (K-562) cell lines. In addition, molecular docking studies were also explored in order to study the probable binding specificity into the active site of Epidermal Growth Factor Receptor tyrosine kinase (EGFR) (PDB ID: 1M17) using Molegro Virtual Docker Evaluation 2013 6.0.1 (MVD). Based on the molecular docking result, it was found that compound 5a exhibited the best interaction with the above target (i.e., EGFR) by interacting with specific amino acid residues such as: Thr 766, Gin 767, Thr 830, Cys 575, Ala 719 and Met 769.

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“…For many years now, we have been actively involved in the search for new selective NMDA antagonists, and we have successfully designed a number of ligands, some of which showed promising neuroprotective activity. [6][7][8][9][10][11][12][13][14] NMDA antagonists are typically characterized by an increase in the distance between the proximal and the distal acidic groups of Glu, e.g. 4-6 carbon atoms.…”

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confidence: 99%

Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

Pinto

Tamborini

Mastronardi

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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3-Carboxy-pyrazolinalanine as a new scaffold for developing potent and selective NMDA receptor antagonists

Cited by 13 publications

References 14 publications

Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

Synthesis, characterization, molecular docking and in vitro anticancer activity of 3-(4-methoxyphenyl)-5-substituted phenyl-2-pyrazoline-1- carbothioamide

Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

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