Design and Synthesis of Novel Potent Antinociceptive Agents: Methyl-imidazolyl N-Acylhydrazone Derivatives

Figueiredo, Juliana M.; Camara, Celso de Amorim; Amarante, Emanuel G; Miranda, Ana Luísa P.; Santos, F. M. dos; Rodrigues, Carlos Rangel; Fraga, Carlos A.M.; Barreiro, Eliezer J.

doi:10.1016/s0968-0896(00)00152-8

Cited by 44 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various substituted derivatives of these heterocycles have shown utility against a range of biological targets. A large number of DHP and related compounds have been reported for their anti-inflammatory activity [1][2][3][4].Some new work is also reported so far on the anti-inflammatory activity of 1,4-dihydropyridines possessing analgesic, [5] hypotensive , , [6] anti-tumor, [7] and coronary dialating activities [8]. Various methodologies have been described for the synthesis of 1,4-dihydropyridines.…”

Section: Introductionmentioning

confidence: 99%

An Efficient One Pot Synthesis of some New 1,4-Dihydropyridine Derivatives Using Multicomponent Reaction

Prajapati

Senjani

Naliapara

2015

ILCPA

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

An Efficient One Pot Synthesis of some New 1,4-Dihydropyridine Derivatives Using Multicomponent Reaction

Prajapati

Senjani

Naliapara

2015

ILCPA

View full text Add to dashboard Cite

show abstract

“…In another study, Cunha et al used aryl-N-acyl hydrazone motif in order to obtain new anti-nociceptive agents, based on the rational basis of the molecular hybridization strategy on aminopyrine, a known pyrazolone (Cunha et al, 2002). Moreover, parasubstitution of aryl-N-acyl hydrazone moiety has been reported as an important structural factor for increasing anti-nociceptive and anti-inflammatory potentials of a chemical compound (Figueiredo et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and anti-nociceptive, anti-inflammatory activities of new aroyl propionic acid derivatives including N-acylhydrazone motif

et al. 2014

View full text Add to dashboard Cite

In the present study, new 4-[4-[2-(2-(4-substituted benzylidene)hydrazinyl)-2-oxoethoxy]phenyl]-4-oxobutanoic acid derivatives were synthesized, and their antinociceptive and anti-inflammatory activities were investigated. In the synthesis of the compounds, 4-[4-(2-ethoxy-2-oxoethoxy)phenyl]-4-oxobutanoic acid molecule was used as starting material. The intermediate hydrazide compound (1) was reacted with appropriate aromatic aldehydes to obtain final hydrazone compounds (2a-i). All final compounds are well characterized by IR, 1 H NMR, 13 C NMR, and MS spectroscopic data. Hot-plate and tail-clip tests, measuring centrally organized responses to a nociceptive stimulus, were performed in order to examine anti-nociceptive potentials of the compounds (50 mg/kg). In addition, peripherally mediated anti-nociceptive effect was assessed by acetic acid-induced writhing tests. Further, carrageenan-induced paw edema method was used in order to evaluate the anti-inflammatory activity potential of the compounds. Motor coordination of the animals was examined in a Rota-rod apparatus. The obtained data indicated that compounds 2a, 2b, 2c, 2d, 2e, 2f decreased the number of acetic acid-induced writhing behaviors comparable with diclofenac sodium (10 mg/kg). The same compounds significantly decreased the paw swelling rate (%) of the mice with respect to the control values. These results indicated that compounds 2a, 2b, 2c, 2d, 2e, and 2f have peripherally mediated anti-nociceptive and antiinflammatory activities. On the other hand, none of the tested compounds changed the reaction time of mice in hotplate or tail-clip tests indicating that neither supraspinal nor spinal pathways were affected. The observed effect seems to be specific, since Rota-rod tests did not point out any motor impairment induced by the test compounds.

show abstract

“…In this paper we focus on the compound 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294, 1), a novel cardioactive compound of the N-acylhydrazone class [14] that was found to improve intracellular Ca 2+ regulation [15] and prevent myocardial infarction induced by cardiac dysfunction, which could potentially prevent heart failure. In addition, (1) also promoted vasodilation in aortic rings, mediated by the guanylate cyclase/cyclic guanylate monophosphate pathway [16].…”

Section: Introductionmentioning

confidence: 99%

Combination of docking, molecular dynamics and quantum mechanical calculations for metabolism prediction of 3,4-methylenedioxybenzoyl-2-thienylhydrazone

et al. 2011

View full text Add to dashboard Cite

In modern drug discovery process, ADME/Tox properties should be determined as early as possible in the test cascade to allow a timely assessment of their property profiles. To help medicinal chemists in designing new compounds with improved pharmacokinetics, the knowledge of the soft spot position or the site of metabolism (SOM) is needed. In silico methods based on docking, molecular dynamics and quantum chemical calculations can bring us closer to understand drug metabolism and predict drug-drug interactions. We report herein on a combined methodology to explore the site of metabolism prediction of a new cardioactive drug prototype, LASSBio-294 (1), using MetaPrint2D to predict the most likely metabolites, combined with structure-based tools using docking, molecular dynamics and quantum mechanical calculations to predict the binding of the substrate to CYP2C9 enzyme, to estimate the binding free energy and to study the energy profiles for the oxidation of (1). Additionally, the computational study was correlated with a metabolic fingerprint profiling using LC-MS analysis. The results obtained using the computational methods gave valuable information about the probable metabolites of (1) (qualitatively) and also about the important interactions of this lead compound with the amino acid residues of the active site of CYP2C9. Moreover, using a combination of different levels of theory sheds light on the understanding of (1) metabolism by CYP2C9 and its mechanisms. The metabolic fingerprint profiling of (1) has shown that the metabolites founded in highest concentration in different species were metabolites M1, M2 and M3, whereas M8 was found to be a minor metabolite. Therefore, our computational study allowed a qualitative prediction for the metabolism of (1). The approach presented here has afforded new opportunities to improve metabolite identification strategies, mediated by not only CYP2C9 but also other CYP450 family enzymes.

show abstract

Design and Synthesis of Novel Potent Antinociceptive Agents: Methyl-imidazolyl N-Acylhydrazone Derivatives

Cited by 44 publications

References 19 publications

An Efficient One Pot Synthesis of some New 1,4-Dihydropyridine Derivatives Using Multicomponent Reaction

An Efficient One Pot Synthesis of some New 1,4-Dihydropyridine Derivatives Using Multicomponent Reaction

Synthesis and anti-nociceptive, anti-inflammatory activities of new aroyl propionic acid derivatives including N-acylhydrazone motif

Combination of docking, molecular dynamics and quantum mechanical calculations for metabolism prediction of 3,4-methylenedioxybenzoyl-2-thienylhydrazone

Contact Info

Product

Resources

About