scholarly journals DESIGN, SYNTHESIS AND BIOLOGICAL SCREENING OF AMINOACETYLENIC TETRAHYDROPHTHALIMIDE ANALOGUES AS NOVEL CYCLOOXYGENASE (COX) INHIBITORS

2017 ◽  
Vol 9 (2) ◽  
pp. 160
Author(s):  
Ahmed Basim ◽  
Zuhair A. Muhi Eldeen ◽  
Elham N. Al-kaissi ◽  
Ghadeer Suaifan ◽  
Mohammad A. Ghattas ◽  
...  
Keyword(s):  
Elemental Analysis ◽  
Inhibitory Activity ◽  
Aryl Group ◽  
Design Synthesis ◽  
Cox Inhibitors ◽  
H Nmr ◽  
Phthalimide Derivative ◽  
Cox 2 ◽  
Cox 1 ◽  
C Nmr

<p><strong>Objective: </strong>To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs.</p><p><strong>Methods: </strong>Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione. The alkylated tetrahydro phthalimide was subjected to Mannich reaction afforded the desired amino acetylenic tetra phthalimide derivatives (AZ 1-6). The elemental analysis was indicated by the EuroEA elemental analyzer and biological characterization was via IR, <sup>1</sup>H-NMR, [13]C-NMR, DSC was determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d<sub>6</sub> as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes.</p><p><strong>Results</strong>:<strong> </strong>The IR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, DSC and elemental analysis were consistent with the assigned structures. The designers of the compounds as COXs inhibitor activity were based on the nationalisation of the important criteria that provide effective inhibitory binding with COXs–receptor. The results indicated that the synthesised compounds (AZ1-6) showed a close similarity in the binding affinity to both COXs and may be more specific to COX-1. AZ-5 showed the highest % of inhibition for COX-1 even better than aspirin. Which may suggest that the aryl group is required for COX-2 inhibition.</p><p><strong>Conclusion: </strong>For the first time, we indicate the requirement of aromaticity in COX-2 structural inhibitory activity. </p>

Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Zafer Sahin ◽  
Yağmur Özhan ◽  
Hande Sipahi ◽  
Sevde Nur Biltekin ◽  
Leyla Yurttaş ◽  
...  
Keyword(s):  
Hydroxy Ketone ◽  
No Production ◽  
Raw 264.7 ◽  
Pyrazole Derivatives ◽  
H Nmr ◽  
Pyrazolone Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1 ◽  
C Nmr

Abstract Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1H NMR, 13C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC50. Rest of the compounds (1, 3–9) showed 10.4–28.1 μM IC50 on COX-2 and 17.0–35.6 μM IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1–9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds (1–9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.

scholarly journals Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long Tang ◽  
Jianchun Jiang ◽  
Guoqiang Song ◽  
Yajing Wang ◽  
Ziheng Zhuang ◽  
...  
Keyword(s):  
Small Molecules ◽  
Inhibitory Activity ◽  
Structural Modification ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
H Nmr ◽  
Lead Compounds ◽  
Activity Test ◽  
Synthesis And Biological Evaluation ◽  
C Nmr

AbstractA series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.

scholarly journals Synthesis and theoretical activity evaluation of a new steroid-oxazolone derivative against COX1-1 and COX-2

2019 ◽  
Vol 9 (4) ◽  
pp. 4107-4113
Keyword(s):  
Elemental Analysis ◽  
Cox Inhibitors ◽  
Activity Evaluation ◽  
Docking Model ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Cox 1

There are some reports for the preparation of several drugs as cyclooxygenase (COX) inhibitors; however, some reagents used in the preparation are expensive and difficult to handle. The aim of this study was to synthesize a steroid-oxazolone derivativeusing some reactions such as i) hydroxylation-amiination; ii) amidation; iii) alkynyl-addition; iv) aldolization and iv) imination. In addition, a theoretical ass was carried out to evaluate the interaction of both COX-1 and COX-2 with the steroid-oxazolone derivativeusing indomethacin and rofecoxib as controls in a docking model. The structure of the compounds obtained was confirmed through elemental analysis, spectroscopy and spectrometry data. The results showed that there are differences between the interaction of the steroidoxazolone derivativewith both COX 1 and COX 2 compared with the bound of indomethacin and rofecoxib with this type of enzymes. These data suggest that the steroid-oxazolone derivativecould be a good candidate as COX-inhibitor translated as a possible drug for treatment of pain.

scholarly journals A new 14,15-dinor-labdane Glucoside from Crassocephalum Mannii

2008 ◽  
Vol 3 (6) ◽  
pp. 1934578X0800300
Author(s):  
Mohamed-Elamir F. Hegazy ◽  
Ashraf A. Aly ◽  
Ahmed A. Ahmed ◽  
Djemgou C. Pierre ◽  
Pierre Tane ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Inhibitory Effect ◽  
H Nmr ◽  
Aerial Parts ◽  
Cox 2 ◽  
Cox 1 ◽  
C Nmr

A new 14,15-dinor-labdane glucoside, named crassoside A (1), was isolated from the aerial parts of Crassocephalum mannii. The structure of 1 was elucidated on the basis of spectroscopic analysis (1H NMR, 13C NMR, HMQC, HMBC and NOEs). Compound 1 demonstrated a low inhibitory effect against COX-1, but was inactive against COX-2.

scholarly journals Synthesis of Isoindoline-1,3-Dione Derivatives as Cyclooxygenase (Cox) S Inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Al-Husseini Jaafar ◽  
Muhi-Eldeen Zuhair ◽  
Al-Tameemi Sadeq ◽  
Al-Qazweeny Rand
Keyword(s):  
Catalytic Amount ◽  
Ligand Efficiency ◽  
Aryl Group ◽  
Ft Ir ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Acetylenic Group ◽  
First Time ◽  
Cox 1 ◽  
C Nmr

Inflammation is the vital part of the immune system's response to injury and infection. It is the body's way of signaling the immune system to heal and repair damaged tissue. The objective of this paper is to design and synthesize a new isoindoline 1,3-dinoe derivative and investigate their selective anti inflammatory activity to COXs. As a potential anti-inflammatory compound, Isoindoline-1,3-dione derivatives were synthesized from the addition reaction of phthalimide, formaldehyde, catalytic amount of potassium hydroxide and cyclic amine in ethanol yielded the desired Isoindoline-1,3-dione compounds (ZJ1-ZJ6. 1H-NMR, ¹³C-NMR, FT-IR and elemental analysis were consistent with the assigned structures. Isoindoline-1,3-dione derivatives exhibited good inhibitory activity against the COX enzymes. To explain the result of our investigation to COX-1 and COX-2 and the selectivity of our compounds to either COX-1 or COX-2, the rationalization in COX-1, the amino group participate more effectively in binding with the ligand while in COX-2, the aryl group is more effective in binding to the ligand. The amino acetylenic compounds behave differently toward COXs from our compound. ZJ4 have shown some selective COX-1 ligand efficiency while ZJ1 promised a potent blockage and ligand efficiency toward the COX-2 enzyme which was found to be higher than the marketed drug Indomethacin and near potency score of Celecoxib. For the first time, this indicates the requirement of investigating the removal of acetylenic group in this study showed that it might be a different binding site in COXs which may result in effective compounds.

scholarly journals SYNTHESIS AND STRUCTURAL ELUCIDATION OF AMINO ACETYLENIC AND THIOCARBAMATES DERIVATIVES FOR 2-MERCAPTOBENZOTHIAZOLE AS ANTIMICROBIAL AGENTS

2017 ◽  
Vol 9 (2) ◽  
pp. 192
Author(s):  
Aseel Alsarahni ◽  
Zuhair Muhi Eldeen ◽  
Elham Al-kaissi ◽  
Ibrahim Al- Adham ◽  
Najah Al-muhtaseb
Keyword(s):  
Antimicrobial Activity ◽  
Elemental Analysis ◽  
Antimicrobial Agents ◽  
Diffusion Method ◽  
Benzothiazole Derivatives ◽  
H Nmr ◽  
Ft Ir ◽  
Potential Antimicrobial Activity ◽  
C Nmr

<p><strong>Objective: </strong>To design and synthesize amino acetylenic and thiocarbonate of 2-mercapto-1,3-benthiazoles as potential antimicrobial agents.</p><p><strong>Methods: </strong>A new series of 2-{[4-(t-amino-1-yl) but-2-yn-1-yl] sulfanyl}-1,3-benzothiazole derivatives (AZ1-AZ6), and S-1,3-benzothiazol-2-yl-O-alkyl carbonothioate derivatives were synthesised, with the aim that the target compounds show new and potential antimicrobial activity. The elemental analysis was indicated by the EuroEA elemental analyzer, and biological characterization was via IR, <sup>1</sup>H-NMR, [13]C-NMR, DSC were determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer using DMSO-d<sub>6</sub> as a solvent.<em> </em><em>In vitro </em>antimicrobial activity, evaluation was done for the synthesised compounds, by agar diffusion method and broth dilution test. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. <em></em></p><p><strong>Results: </strong>The IR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, DSC and elemental analysis were consistent with the assigned structures. Compound of 2-{[4-(4-methylpiperazin-1-yl)but-2-yn-1-yl] sulfanyl}-1,3-benzothiazole (AZ1), 2-{[4-(2-methylpiperidin-1-yl)but-2-yn-1-yl]sulfanyl}-1,3-benzothiazole (AZ2), 2-{[4-(piperidin-1-yl) but-2-yn-1-yl]sulfanyl}-1, 3-benzothiazole (AZ6), S-1,3-benzothiazol-2-yl-O-ethyl carbonothioate (AZ7), and S-1,3-benzothiazol-2-yl-O-(2-methylpropyl) carbonothioate (AZ9) showed the highest antimicrobial activity against <em>Pseudomonas aeruginosa </em>(<em>P. aeruginosa</em>), AZ-9 demonstrated the highest antifungal activity against <em>Candida albicans </em>(<em>C. albicans</em>), with MIC of 31.25 µg/ml.</p><p><strong>Conclusion: </strong>These promising results promoted our interest to investigate other structural analogues for their antimicrobial activity further.</p>

[Zn(phen)2(CX3COO)]+, X = H orCl; Influence of X on the Coordination Mode of the Carboxylate Group (phen = 1,10-Phenanthroline)

2005 ◽  
Vol 60 (10) ◽  
pp. 1049-1053 ◽  
Author(s):  
Zeanab Talaei ◽  
Ali Morsali ◽  
Ali R. Mahjoub
Keyword(s):  
Nmr Spectroscopy ◽  
Elemental Analysis ◽  
Coordination Mode ◽  
Bidentate Ligand ◽  
Carboxylate Group ◽  
X Ray ◽  
X Ray Crystallography ◽  
H Nmr ◽  
Coordinate Geometry ◽  
C Nmr

Two new ZnII(phen)2 complexes with trichloroacetate and acetate anions, [Zn(phen)2(CCl3COO)- (H2O)](ClO4) and [Zn(phen)2(CH3COO)](ClO4), have been synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR spectroscopy. The single crystal X-ray data of these compounds show the Zn atoms to have six-coordinate geometry. From IR spectra and X-ray crystallography it is established that the coordination of the COO− group is different for trichloroacetate and acetate. The former acts as a monodentate whereas the latter acts as a bidentate ligand.

Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and response to released ATP

2001 ◽  
Vol 281 (2) ◽  
pp. C524-C531 ◽  
Author(s):  
Rennolds S. Ostrom ◽  
Caroline Gregorian ◽  
Ryan M. Drenan ◽  
Kathryn Gabot ◽  
Brinda K. Rana ◽  
...  
Keyword(s):  
Cell Function ◽  
Mdck Cells ◽  
Second Messengers ◽  
Atp Release ◽  
Cox Inhibitors ◽  
Cox 2 ◽  
Factor Α ◽  
Biochemical Activation ◽  
Camp Formation ◽  
Cox 1

Madin-Darby canine kidney (MDCK) cells release ATP upon mechanical or biochemical activation, initiating P2Y receptor signaling that regulates basal levels of multiple second messengers, including cAMP ( J Biol Chem 275: 11735–11739, 2000). Data shown here document inhibition of cAMP formation by Gd3+ and niflumic acid, channel inhibitors that block ATP release. cAMP production is stimulated via Ca2+-dependent activation of cytosolic phospholipase A2, release of arachidonic acid (AA), and cyclooxygenase (COX)-dependent production of prostaglandins, which activate prostanoid receptors coupled to Gs and adenylyl cyclase. In the current investigation, we assessed the expression and functional role of the two known isoforms of COX, COX-1 and COX-2. Treatment of cells with either a COX-1-selective inhibitor, SC-560, or COX-2-selective inhibitors, SC-58125 or NS-398, inhibited basal and UTP-stimulated cAMP levels. COX inhibitors also decreased forskolin-stimulated cAMP formation, implying this response is in part attributable to an action of AA metabolites. These findings imply an important role for the inducible form of COX, COX-2, under basal conditions. Indeed, COX-2 expression was readily detectable by immunoblot, and treatments that induce or reduce COX-2 expression in other cells (interleukin-1β, tumor necrosis factor-α, phorbol ester, or dexamethasone) had minimal or no effect on the levels of COX-2 immunoreactivity. RT-PCR using isoform-specific primers detected COX-2 mRNA. We conclude that COX-2 is constitutively expressed in MDCK-D1 cells and participates in basal and P2Y2-mediated signaling, implying a key role for COX-2 in regulation of epithelial cell function.

scholarly journals Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 554 ◽  
Author(s):  
Harshal Nemade ◽  
Aviseka Acharya ◽  
Umesh Chaudhari ◽  
Erastus Nembo ◽  
Filomain Nguemo ◽  
...  
Keyword(s):  
Wnt Signaling Pathway ◽  
Calcium Transient ◽  
Cardiac Differentiation ◽  
Cyclooxygenase Inhibitors ◽  
Cox Inhibitors ◽  
Screening Model ◽  
Cox 2 ◽  
Transient Measurements ◽  
Cox 1

Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, the Wingless (Wnt) signaling pathway has emerged as the key regulator of cardiomyogenesis. In this study, we evaluated the effects of cyclooxygenase inhibitors on cardiac differentiation of hPSCs. Cardiac differentiation was performed by adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency of cardiac differentiation was evaluated by flow cytometry and RT-qPCR. Generated hPSC-CMs were characterised using immunocytochemistry, electrophysiology, electron microscopy, and calcium transient measurements. Our data show that the COX inhibitors Sulindac and Diclofenac in combination with CHIR99021 (GSK-3 inhibitor) efficiently induce cardiac differentiation of hPSCs. In addition, inhibition of COX using siRNAs targeted towards COX-1 and/or COX-2 showed that inhibition of COX-2 alone or COX-1 and COX-2 in combination induce cardiomyogenesis in hPSCs within 12 days. Using IMR90-Wnt reporter line, we showed that inhibition of COX-2 led to downregulation of Wnt signalling activity in hPSCs. In conclusion, this study demonstrates that COX inhibition efficiently induced cardiogenesis via modulation of COX and Wnt pathway and the generated cardiomyocytes express cardiac-specific structural markers as well as exhibit typical calcium transients and action potentials. These cardiomyocytes also responded to cardiotoxicants and can be relevant as an in vitro cardiotoxicity screening model.

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