Dual Anti-Inflammatory and Anti-Bacterial Effects of Phenylhydrazide and Phenylhydrazone Derivatives (original) (raw)
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In the present study, a series of 4-hydroxy-Nʹ-[(1E)-substituted-phenylmethylidene] benzohydrazide analogs was synthesized, characterized, and evaluated for their antibacterial and anti-oxidant activity. All the tested compounds show high antibacterial activity with compound AR 7 , Nʹ-(3,4,5-trimethoxybenzylidene)-4-hydroxybenzohydrazide as the most active compound, whereas compounds AR 10 (hydrogen peroxide scavenging) and AR 8 (2,2-diphenyl-1picrylhydrazyl radical scavenging activity method) were found to possess maximum anti-oxidant activity indicating that different mechanisms are involved in different anti-oxidant determination methods.
Journal of medicinal chemistry, 2017
The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727,842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 µM. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(1-((2,3-dihydro-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhib...
ACS Medicinal Chemistry Letters, 2016
The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.
Archives of biochemistry and biophysics, 2014
Myeloperoxidase (MPO) catalyzes the breakdown of hydrogen peroxide and the formation of the potent oxidant hypochlorous acid. We present the application of the fluorogenic peroxidase substrate 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) in steady-state and transient kinetic studies of MPO function. Using initial kinetic parameters for the MPO system, we characterized under the same conditions a number of gold standards for MPO inhibition, namely 4-amino benzoic acid hydrazide (4-ABAH), isoniazid and NaN3 before expanding our focus to isomers of 4-ABAH and benzoic acid hydrazide analogs. We determined that in the presence of hydrogen peroxide that 4-ABAH and its isomer 2-ABAH are both slow-tight binding inhibitors of MPO requiring at least two steps, whereas NaN3 and isoniazid-based inhibition has a single observable step. We also determined that MPO inhibition by benzoic acid hydrazide and 4-(trifluoromethyl) benzoic acid hydrazide was due to hydrolysis of the ester bond between MPO h...
Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates
Journal of Biological Chemistry, 2013
Background: Myeloperoxidase causes oxidative damage in many inflammatory diseases. Results: New substituted aromatic hydroxamates are identified as potent, selective, and reversible inhibitors of MPO. Conclusion: Binding affinities of hydroxamates to the heme pocket determine the potency of inhibition. Significance: Compounds that bind tightly to the active site of myeloperoxidase have potential as therapeutically useful inhibitors of oxidative stress.
European Chemical Bulletin, 2020
In the investigation, a series of new pyridyl and thiazolyl clubbed hydrazone derivatives have been synthesized. The newly synthesized compounds were evaluated for their in vitro antimicrobial and antioxidant activities. Some among the compounds have shown excellent antimicrobial activity against both bacterial and fungal pathogens. Two compounds among the series have exhibited excellent antioxidant activity. Furthermore, a molecular docking study has been performed against DNA gyrase to know the binding modes of these molecules and recorded good binding affinity. The ADME study has also been performed for predicting the pharmacokinetic profile, which expressed good oral drug-like behaviour.
Molecular docking studies of 1,3,4 -thiadiazoles as myeloperoxidase inhibitors
2021
Myeloperoxidase (MPO) is a heterodimeric, cationic and glycosylated haeme enzyme which gets released under increased oxidative stress producing neutrophil oxidant, hypochlorous acid having the capacity to modify various biomolecules by chlorination and/or oxidation of sulfhydryl groups in proteins causing their inactivation and promoting inflammatory tissue damage. Different levels of hypochlorus acid are used as a trait marker for prescribing the disorders e.g. atherosclerosis, rheumatoid arthritis, lung cancer, Immuno-reactivity. Mini library of 22500 2,5disubstituted 1,3,4 thiadiazoles were docked with Myeloperoxidase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking process. Keeping this fact in view, critical evaluation of the performance was performed by GLIDE by HTVS, SP and XP. The ADME parameters by QIKPROP and protein-ligand binding free energies were calculated using th...
Egyptian Journal of Chemistry, 2019
T HE inevitable consequence of the widespread use of antimicrobial agents has been the emergence of antibiotic resistant pathogens, functioning an ever-increasing used for new drugs. In an effort to develop antimicrobial agents a series of hydrazones derivative (4a-e) were synthesized from chalcones. Substituted hydrazides were reacted with chalcone in the presence of acetic acid and hydrazone derivatives were synthesized. The synthesized hydrazones were characterized on the basis physical and spectroscopic data and were evaluated for their antimicrobial activity against various bacterial and fungal strains using disc diffusion method using nutrient agar media. In addition, the antinociceptive activities of the products were evaluated. Our data showed that many derivatives have promising activities as antinocicepative agents.Furthermore the assessment of structural similarity of the target compounds with various standard drugs was done. Evaluation of the compounds revealed remarkable antibacterial, antifungal and antioxidant activity. In addition, an in silico docking study was performed in order to explain the possible interactions and the docking scores of all the compounds into the crystal structure of DNA Gyrase (Pdb code : 3U2D) using Online docking server program.
Letters in Applied Microbiology, 2022
The emergence of resistance to antibacterial drugs remains an important global threat that necessitates an urgent need for the discovery of alternative drugs. This study was undertaken to synthesize some novel nitroaryl/heteroaryl hydrazone derivatives as potential antibacterial agents. After synthesizing by a simple reaction between quinoline/quinazoline hydrazine and nitroaryl/heteroaryl aldehydes, all the compounds were screened for their antibacterial activities, cytotoxicity and in silico investigations. The compound, 2-(4-nitrobenzylidene)-1-(quinazolin-4-yl)hydrazine (1b), displayed significant antimicrobial activity against several susceptible and resistant bacteria without any cytotoxicity. Moreover, scanning electron microscopy (SEM) revealed the complete destruction of Staphylococcus aureus and Escherichia coli following exposure to this compound after 2 h exposure. The in silico studies confirmed the better binding energy of these compounds in comparison with the referen...
Molecules (Basel, Switzerland), 2016
Some novel hydrazone derivatives 6a-o were synthesized from the key intermediate 4-Chloro-N-(2-hydrazinocarbonyl-phenyl)-benzamide 5 and characterized using IR, ¹H-NMR, (13)C-NMR, mass spectroscopy and elemental analysis. The inhibitory potential against two secretory phospholipase A₂ (sPLA₂), three protease enzymes and eleven bacterial strains were evaluated. The results revealed that all compounds showed preferential inhibition towards hGIIA isoform of sPLA₂ rather than DrG-IB with compounds 6l and 6e being the most active. The tested compounds exhibited excellent antiprotease activity against proteinase K and protease from Bacillus sp. with compound 6l being the most active against both enzymes. Furthermore, the maximum zones of inhibition against bacterial growth were exhibited by compounds; 6a, 6m, and 6o against P. aeruginosa; 6a, 6b, 6d, 6f, 6l, 6m, 6n, and 6o against Serratia; 6k against S. mutans; and compounds 6a, 6d, 6e, 6m, and 6n against E. feacalis. The docking simulat...