1,5-Diarylpyrazole and vanillin hybrids: Synthesis, biological activity and DFT studies

Hernández‐Vázquez, Eduardo; Castañeda‐Arriaga, Romina; Ramírez-Espinosa, Juan José; Medina-Campos, Omar Noel; Hernández‐Luis, Francisco; Chaverrí, José Pedraza; Estrada-Soto, Samuel

doi:10.1016/j.ejmech.2015.06.010

Cited by 30 publications

(21 citation statements)

References 46 publications

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“…Once acquired NMR spectra, the E-geometry was definitively assigned on the basis of the CONH group proton atom chemical shift (δ 11.23 ppm), in accordance to the literature data. In this regard, to a series of hydrazone derivatives, having signals of the NH group <12 ppm as in our case, the E configuration was assigned by NOESY experiments and DFT calculations [31]. Furthermore, it was also reported that NH chemical shift for Z isomers is instead moved to much higher delta values (δ > 15.5 ppm) [32].…”

Section: Ros Production and Aggregation Inhibition Evaluated In Humansupporting

confidence: 55%

New Hybrid Pyrazole and Imidazopyrazole Antinflammatory Agents Able to Reduce ROS Production in Different Biological Targets

et al. 2020

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Several anti-inflammatory agents based on pyrazole and imidazopyrazole scaffolds and a large library of substituted catechol PDE4D inhibitors were reported by us in the recent past. To obtain new molecules potentially able to act on different targets involved in inflammation onset we designed and synthesized a series of hybrid compounds by linking pyrazole and imidazo-pyrazole scaffolds to differently decorated catechol moieties through an acylhydrazone chain. Some compounds showed antioxidant activity, inhibiting reactive oxygen species (ROS) elevation in neutrophils, and a good inhibition of phosphodiesterases type 4D and, particularly, type 4B, the isoform most involved in inflammation. In addition, most compounds inhibited ROS production also in platelets, confirming their ability to exert an antiinflammatory response by two independent mechanism. Structure–activity relationship (SAR) analyses evidenced that both heterocyclic scaffolds (pyrazole and imidazopyrazole) and the substituted catechol moiety were determinant for the pharmacodynamic properties, even if hybrid molecules bearing to the pyrazole series were more active than the imidazopyrazole ones. In addition, the pivotal role of the catechol substituents has been analyzed. In conclusion the hybridization approach gave a new serie of multitarget antiinflammatory compounds, characterized by a strong antioxidant activity in different biological targets.

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Section: Ros Production and Aggregation Inhibition Evaluated In Humansupporting

confidence: 55%

New Hybrid Pyrazole and Imidazopyrazole Antinflammatory Agents Able to Reduce ROS Production in Different Biological Targets

et al. 2020

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“…DPPH is a stable free radical that can easily be converted into a stable molecule after the acceptance of an electron or hydrogen radical. It is well documented that the DPPH radical‐scavenging antioxidant activity assay proceeds through a single‐electron‐transfer (SET) or hydrogen‐atom‐transfer (HAT) mechanism –. The DPPH molecule shows a strong absorption band at λ =515 nm in MeOH solution with a deep‐purple color and having an odd electron configuration.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design, Synthesis, Structure–Activity Relationships, Biological Evaluations, and in silico Molecular Docking Studies

et al. 2018

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To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH , OC H , OC H ) functional groups at C1/C2 of ring A and an acyl (COCH and COPh) or phenylsulfonyl (SO Ph and SO C H -3-CH ) functionality at the N6 position of ring B of the aporphine scaffold were synthesized and evaluated for their arachidonic acid (AA)-induced antiplatelet aggregation inhibitory activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical-scavenging antioxidant activity, with acetylsalicylic acid and ascorbic acid as standard references, respectively. The preliminary structure-activity relationship related to AA-induced platelet aggregation inhibitory activity results showed that the aporphine analogues 1-[1,2,9,10-tetramethoxy-6a,7-dihydro-4H-dibenzo[de,g]quinolin-6(5H)-yl]ethanone and 1-[2-(benzyloxy)-1,9,10-trimethoxy-6a,7-dihydro-4H-dibenzo[de,g]quinolin-6(5H)-yl]ethanone to be the best compounds of the series. Moreover, the DPPH free-radical-scavenging antioxidant activity results demonstrated that the aporphine analogues 1,2,9,10-tetramethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, 2-ethoxy-1,9,10-trimethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, 1-ethoxy-2,9,10-trimethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, 2,9,10-trimethoxy-6-(methylsulfonyl)-1-propoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline, and 1-(benzyloxy)-2,9,10-trimethoxy-6-(methylsulfonyl)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline were the best compounds of the series. Moreover, in silico molecular docking simulation studies of the active analogues were also performed.

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“…Notably, unsubstituted phenyl-containing analogues 10 q and 10 r showed highera ctivity than monohydroxylated congener 10 g (69.1 and 40.2 %i nhibition, respectively). We then becamei nterested in inspectingt he influence of the methoxy groups in the global anti-inflammatory effect.I tw as soon discoveredt hat those oxygenated substituents hada nu nfavorable effect on the activity,a nd trimethoxylated variants 10 a-d (percentage of inhibition of 34.9-44.2 %) were found to be less effective than dimethoxylated 10 f (56.1 %i nhibition) and slightly more effective monomethoxylated 10 e with 64.3 % edemar eduction.C uriously,c ompounds 10 i-l bearing av anillin scaffold, contrary to the expecteda ctivity due to their antioxidantp roperties, [23] were not the most active pyrazinones. The same finding was achieved with syringaldehyded erivatives 10 m-o.T hese outcomes indicated that, presumably,a ntioxidantactivity is not correlated to the anti-inflammatory activity and that it is more likely relatedt oareceptor-binding effect.…”

Section: Anti-inflammatory Evaluation Through the Tpa-induced Mouse Ementioning

confidence: 87%

A Two‐Step Multicomponent Synthetic Approach and Anti‐inflammatory Evaluation of N‐Substituted 2‐Oxopyrazines

et al. 2018

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Inflammation is widely reported as a main factor for the development of chronic diseases such as cancer, diabetes, and even metabolic syndrome. Thus, the search for novel anti‐inflammatory compounds is required. Herein we describe the synthesis of a collection of peptidic pyrazinones by a convenient approach involving a multicomponent isocyanide‐based reaction followed by a tandem deprotection/oxidative cyclization step. This series of compounds were tested for their potential anti‐inflammatory capacity in an in vivo murine model, and four compounds were identified to inhibit tetradecanoylphorbol acetate (TPA)‐induced edema by more than 75 %. The two most active compounds, N‐benzyl‐2‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐2‐[2‐oxopyrazin‐1(2H)‐yl]acetamide (10 o) and N‐cyclohexyl‐2‐[2‐oxopyrazin‐1(2H)‐yl]‐2‐[4‐(trifluoromethyl)phenyl]acetamide (10 x), with methyl and trifluoromethyl groups, were also able to decrease myeloperoxidase activity and leukocyte infiltration. Moreover, 10 x decreased the thickness of TPA‐treated mouse ears, as observed in histological analysis of the tissues.

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1,5-Diarylpyrazole and vanillin hybrids: Synthesis, biological activity and DFT studies

Cited by 30 publications

References 46 publications

New Hybrid Pyrazole and Imidazopyrazole Antinflammatory Agents Able to Reduce ROS Production in Different Biological Targets

New Hybrid Pyrazole and Imidazopyrazole Antinflammatory Agents Able to Reduce ROS Production in Different Biological Targets

Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design, Synthesis, Structure–Activity Relationships, Biological Evaluations, and in silico Molecular Docking Studies

A Two‐Step Multicomponent Synthetic Approach and Anti‐inflammatory Evaluation of N‐Substituted 2‐Oxopyrazines

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