Benzoic Acid Hydrazide Research Articles

Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and Structure Activity Relationships of Inhibitors.

Inflammation is an initial response of the body to a harmful stimuli and it is achieved by the increased movement of leukocytes (especially granulocytes) from blood into injured tissues. It is required for healing wounds and infections. Despite their indispensable role in microbial killing, the inflammation reactions may also cause diseases to a host such as hay fever, atherosclerosis, and rheumatoid arthritis. The enzymes and oxidizing species released during the inflammatory process can cause damages to the host tissues which lead to inflammatory syndromes. The role of myeloperoxidase (MPO) in the inflammatory reactions is well documented. It contributes in killing the pathogens but it is also implicated in several inflammatory syndromes such as Parkinson's disease, Alzheimer's disease and atherosclerosis. Thus, this enzyme has attracted more attention of the scientists and it has become a target for drug designing. In the last decade, several reversible and irreversible MPO inhibitors were identified as very high potent inhibitors such as fluoroalkylindole, aromatic hydroxamic acid, thioxanthine and benzoic acid hydrazide derivatives. In this review, we tried to illustrate the MPO inhibitors and highlight their structure activity relationship (SAR). In this paper we also discussed the mechanism of the inhibitory effect of the most potent compounds.

Substituent group effects on the self-assembly of oxovanadium(V) complexes with hydrazone ligands bearing benzoic acid (1-methyl-3-oxobutylidene)hydrazide backbones

An oxo-bridged dinuclear oxovanadium(V) complex, [V2O2(μ-O)(L1)2] (1) [H2L1 = 3-nitrobenzoic acid (1-methyl-3-oxobutylidene)hydrazide], and a mononuclear oxovanadium(V) complex, [VO(OMe)(L2)] (2) [H2L2 = 3-hydroxynaphthalene-2-carboxylic acid (1-methyl-3-oxobutylidene)hydrazide], were prepared by the reactions of [VO(acac)2] with H2L1 and H2L2, respectively, in methanol. Both complexes were characterized by elemental analysis, IR spectra, and single crystal X-ray crystallography. The crystal of 1 crystallizes in the monoclinic space group P2/n, with a = 13.116(3) A, b = 7.597(2) A, c = 13.927(2) A, β = 104.851(2)°, V = 1341.4(5) A3, Z = 2. The crystal of 2 crystallizes in the triclinic space group \(P\overline 1 \), with a = 7.897(2) A, b = 9.690(2) A, c = 11.576(3) A, α = 86.405(2)°, β = 70.597(2)°, γ = 85.991(2)°, V = = 832.7(3) A3, Z = 2. The V atoms in the complexes have square pyramidal environment. The substituent groups attached to the aromatic rings can influence the self-assembly of the complexes.

Tuning of Aggregation Enhanced Emission and Solid State Emission from 1,8-Naphthalimide Derivatives: Nanoaggregates, Spectra, and DFT Calculations.

Four new 1,8-naphthalimide based compounds, 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoic acid (LH), 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoic acid methyl ester (LMe), 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoyl chloride (LCl), and 4-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylmethyl)-benzoic acid hydrazide (LN) are synthesized and characterized using spectral data and X-ray crystallography. They form nanoaggregates in aqueous-DMF solution and exhibited aggregation enhanced emission. The nanoaggregates are characterized using their scanning electron and atomic force microscopy images. The emission intensity follows the order as LH > LMe > LCl > LN. Their photophysical properties are recorded both in solution and in the solid-state and are correlated with the nature of benzoic acid derivatives owing to the combinatorial effect of π-π stacking and intermolecular and intramolecular interactions. The density functional theory calculations empower the understanding of their molecular and cumulative electronic behaviors. Antiparallel dimeric interactions in the solid-state extend a herringbone arrangement to LH and 2D channel and stair-like arrangement for LCl and LN, respectively.

Optimization of conditions for synthesizing sulfonated hydrazides of benzoic and benzenesulfonic acids

The kinetic relationships of arenesulfonation of benzoic and benzenesulfonic acid hydrazides were studied. Based on the data obtained, the conditions for synthesizing these products were optimized. The synthesis can be performed using aqueous-organic solvents containing 2-propanol, 1,4-dioxane, or tetrahydrofuran as nonaqueous component. The thermal stability of benzenesulfohydrazide and its sulfonation product was compared on the basis of data of gas chromatography–mass spectrometry. The fragmentation pathways of the reactants and target product, sulfonated benzenesulfohydrazide, were suggested.

Anti-inflammatory activity of (2E,15E)-2-[1-(2-aminophenyl)ethylidineamino]-N′-[1-(2-aminophenyl)ethylidene]benzoic acid hydrazide (AEBH) and some of its nanoparticles rare earth complexes

Complexes of Er(III), Gd(III), and La(III) with (2E,15E)-2-[1-(2-aminophenyl)ethylidineamino]-N′-[1-(2-aminophenyl)ethylidene]benzoic acid hydrazide (AEBH) have been synthesized. The isolated complexes were characterized by elemental analyses, thermal analyses (TGA, DTA), IR, 1H NMR, 13C NMR, ES-MS, TEM, and conductance measurements. The results indicated that the ligand coordinates to La(III), Gd(III), and Er(III) in the keto form as neutral pentadentate ligand. The particle size and morphology have been determined by TEM. In vivo pharmacological evaluation of the synthesized compounds in collagen II—Freund’s adjuvant model proved the presence of anti-inflammatory and analgesic activities of these compounds. Gd(III) complex showed higher effect in comparison with the well-known drug meloxicam.

Inactivation of myeloperoxidase by benzoic acid hydrazide

Myeloperoxidase (MPO) is expressed by myeloid cells for the purpose of catalyzing the formation of hypochlorous acid, from chloride ions and reaction with a hydrogen peroxide-charged heme covalently bound to the enzyme. Most peroxidase enzymes both plant and mammalian are inhibited by benzoic acid hydrazide (BAH)-containing compounds, but the mechanism underlying MPO inhibition by BAH compounds is largely unknown. Recently, we reported MPO inhibition by BAH and 4-(trifluoromethyl)-BAH was due to hydrolysis of the ester bond between MPO heavy chain glutamate 242 (HCGlu242) residue and the heme pyrrole A ring, freeing the heme linked light chain MPO subunit from the larger remaining heavy chain portion. Here we probed the structure and function relationship behind this ester bond cleavage using a panel of BAH analogs to gain insight into the constraints imposed by the MPO active site and channel leading to the buried protoporphyrin IX ring. In addition, we show evidence that destruction of the heme ring does not occur by tracking the heme prosthetic group and provide evidence that the mechanism of hydrolysis follows a potential attack of the HCGlu242 carbonyl leading to a rearrangement causing the release of the vinyl-sulfonium linkage between HCMet243 and the pyrrole A ring.

Synthesis, Reactions, and Pharmacological Evaluations of Some Novel Pyridazolopyridiazine Candidates

Herein, we report the synthesis, characterization, and preliminary pharmacological activity of a new series of substituted pyrazolopyridazine derivatives. Compound 1 was reacted with ethoxymethylene malononitrile 2 in refluxing ethanol to give the corresponding compound 3, which was treated with hydrazine hydrate or formamide to give pyrazolo[3,4‐c]pyrazole 4 and pyrazolo pyrimidine 5 derivatives, respectively. Also, compound 3 was reacted with NH4SCN or carbon disulphide or ethyl acetoacetate to yield the corresponding pyrazolo derivatives 6, 7, 8, respectively. Additionally, compound 3 was reacted with triethyl orthoformat in acetic anhydride to give 9, which was treated with hydrazine hydrate to give hydrazino derivative 10. The latter compound transformed into the pyrazolo[4,3‐e][1,2,4]triazolo[1,5‐c]‐pyrimidine 11 via refluxing with acetic anhydride. Finally, compound 9 was reacted with benzoic acid hydrazide or mercapto acetic acid to give compounds 12 and 13, respectively. The latter compound was treated with refluxing ethanolic sodium ethoxide solution to afford the pyrazolothiazolopyrimidine 14. Some of the compounds exhibited better activities as anti‐inflammatory and antimicrobial agents than the reference controls. The detailed synthesis, spectroscopic data, anti‐inflammatory, and antimicrobial activities of the synthesized compounds was reported.

Ordered cleavage of myeloperoxidase ester bonds releases active site heme leading to inactivation of myeloperoxidase by benzoic acid hydrazide analogs

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 heavy chain Glu 242 residue and the heme pyrrole A ring, freeing the light chain and heme b fragment from the larger remaining MPO heavy chain. This new mechanism would essentially indicate that the benzoic acid hydrazide analogs impart inhibition through initial ejection of the heme catalytic moiety without prior loss of the active site iron.

Synthesis and antimicrobial evaluation of some novel benzoimidazole Schiff′s bases and their C-nucleoside derivatives

Background and objectives The discovery of C-nucleosides and continuous study of their biological activities led us to construct new compounds containing 4-(5-benzoyl-benzoimidazol-2)-benzoic acid hydrazide Schiff's bases incorporated into different aldoses, thiazolidinones, and/or their C-nucleoside analogues. The aim of this study is to describe the synthesis of some new heterocycles derived from 4-(5-benzoyl-benzoimidazol-2)-benzoic acid hydrazide and to evaluate their antimicrobial activities. Materials and methods The starting material 4-(5-benzoyl-1H-benzoimidazol-2-yl)-benzonitrile ( 2 ) was prepared through the reaction of (3,4-diamino-phenyl)-phenyl-methanone ( 1 ) with 4-cyanobenzaldehyde in absolute ethanol. Stirring compound 2 with 70% sulfuric acid yielded benzoic acid derivative 3 , followed by esterification and refluxing with hydrazine hydrate to yield the corresponding 4-(5-benzoyl-1H-benzoimidazol-2-yl)-benzoic acid hydrazide ( 5 ). A series of Schiff's bases derivatives 6a-c and 8a-e were prepared by condensation of hydrazide 5 with different monosaccharides and/or with arenaldehydes. Treatment of 6a-c with thioglycolic acid led to the formation of the C-nucleosides ( 7a-c ), whereas treatment of 8a-e with thioglycolic acid yielded the corresponding 2-arylthiazolidin-4-one ( 9a-e ). Results and conclusion Compound 6b showed the highest antimicrobial activity against Bacillus subtilis , Staphylococcus aureus (gram-positive bacteria), Escherichia coli , and Pseudomonas aeuroginosa (gram-negative bacteria), and Candida albicans and Aspergillus niger (fungi) .

Synthesis and antimicrobial activity of some amino acids and sulfamoyl and pyrrole derivatives attached to 4-benzoimidazol-2-yl moiety

Background and objectivesBenzoimidazole moiety is one of the heterocyclic compounds that plays a vital role in biological fields such as antioxidant, antidepressant, anticonvulsant, antimicrobial and anticancer. The aim of this study was to construct new compounds containing 4-(5-benzoyl-benzoimidazol-2) moiety incorporated into different amino acids and sulfamoyl and/or pyrrole analogues and to evaluate their antimicrobial activities.Materials and methodsThe starting material 4-(5-benzoyl-1H-benzoimidazol-2-yl)-benzonitrile ( 2 ) was prepared through the reaction of (3,4-diamino-phenyl)-phenyl-methanone ( 1 ) with 4-cyanobenzaldehyde in absolute ethanol. Stirring compound 2 with 70% sulfuric acid gave benzoic acid derivative 3 followed by esterification and refluxing with hydrazine hydrate to form the corresponding 4-(5-benzoyl-1H-benzoimidazol-2-yl)-benzoic acid hydrazide ( 5 ). A series of derivatives 6a-d were prepared by coupling of benzoic acid derivative 3 with different amino acids ethyl ester. Reacting ester compound 4 with different amines and sulfa drugs led to the formation of the amides derivatives 7a,b and 8a,b , whereas on reacting the hydrazide compound 5 with different acid anhydrides, cyclohexane-1,4-dione and 5-nitroisatin compounds 9a-c , 10 and 11 were obtained.Results and conclusionMost of the test compounds were found to be significantly effective against Bacillus subtilis and Staphylococcus aureus (gram-positive bacteria), Escherichia coli and Pseudomonas aeuroginosa (gram-negative bacteria) and Candida albicans and Aspergillus niger (fungi) .

Synthesis and Biological Screening of New Derivatives of 2,3-dihydro quinazolin-4(1H)-one and Benzotriazepin- 5(2H)-one for Central Nervous System Activity

A new syntheses of novel series of 2,3-dihydroquinazolin-4(1H)-one and benzotriazepin- 5(2H)-one derivatives, starting from the same intermediate (IIa-g). By varying the substituent on the benzamide moiety of the key intermediate (IIa-g) or the conditions of the reactions utilized in this syntheses, the reaction gives rise either quinazolin-4(1H)-one or benzotriazepine-5(2H)-one. The intermediate; 2-methylamino-N-(substituted benzoyl)benzohydrazide (IIa-g); was prepared by condensation of N-methyl-isatoic anhydride with different benzoic acid hydrazides. Constructing the intermediates (IIa-g) on different cyclo-condensation reactions; either with ethylchloroformate /potassium hydroxide or carbon disulfide/potassium hydroxide, yielded a new series of benzotriazepin-5(2H)-one (IIIa-b, IVa-d) and a new series of quinazolin4(1H)-one (Va-c, VI a-d). Pharmacological screening of the new benzotriazepinone derivatives revealed that the compounds (VI a-b, IVc-d) exhibited strong CNS depressant activity over clozapine while compounds (VIa,IVc) showed the same antipsychotic activity as clozapine with an observed neurotoxicity.

Intramolecular Hydrogen Bonding of a Chloride Acceptor Supported by a Dinuclear Nickel(II) Complex with N‐Salicylidene Hydrazide Ligand: Crystal Structure and Magnetic Properties

AbstractThe dinuclear phenoxido‐bridged nickel(II) complex [{Ni(Hsalhyph)Cl(H2O)}2] with the hydrazone ligand H2salhyph, derived from salicylaldehyde and benzoic acid hydrazide, has been synthesized and structurally characterized. The dinuclear Ni2O2 core unit of the complex facilitates the formation of intramolecular O–H···Cl hydrogen bonds. The chlorido ligand is involved in additional N–H···Cl hydrogen bonding leading to an aggregation of the dinuclear complexes forming one‐dimensional staged chains. Within the chains the supramolecular structure is governed by hydrogen bonding and π–π‐stacking interactions. In the crystal structure two additional DMF molecules of crystallization are present per dinuclear complex. The DMF molecules are located between the chains and involved in O–H···O=C hydrogen bonding with the aqua ligands of the dinickel core. Magnetic susceptibility measurements show the presence of antiferromagnetic exchange interactions (H = –JS1S2) with J = –14.8 cm–1 between the nickel(II) ions and indicate a zero‐field‐splitting of D = 12.6 cm–1.

Microwave Promoted Synthesis of 2-(1H-Benzoimidazol-2-Yl-4-Phenol)-5-Aryl-1,3,4-Oxadiazoles

A series of 2-(1H-benzoimidazol-2-yl-4-phenol)-5-aryl-1,3,4-oxadiazoles by the reaction of 3-(1H-benzoimidazol-2-yl)-4-hydroxy-benzoic acid, prepared from 3-formyl-4-hydroxy-benzoic acid and o-phenylendiamine in the presence of sodium bisulfite, with (un) substituted benzoic acid hydrazides using PEG supported dichlorophosphate as dehydration reagent under microwave-accelerated solvent-free condition has been developed. Structures of the corresponding products were elucidated by IR and 1HNMR spectra and elemental analysis.

Synthesis and molecular modeling studies of novel pyrrole analogs as antimycobacterial agents

In the present investigation, a series of 4-(4-pyrrol-1-yl/2,5-dimethyl-4-pyrrol-1-yl) benzoic acid hydrazide analogs, some derived oxadiazoles and azines have been synthesized in good yields and structures of these compounds were established by IR, 1H NMR, 13C NMR, mass spectral and elemental analysis. The newly synthesized title compounds were evaluated for their antimicrobial as well as antimycobacterial activities. Among the tested compounds, 6j and 9c displayed promising anti-tubercular activity. Further, some compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines and A549 (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit anti-tubercular activity at non-cytotoxic concentrations. The docking of inhibitors into InhA using Sybyl-X 2.0 software revealed the vital interactions and binding conformation of the inhibitors.

Synthesis and Biological Evaluation of Some NewN1-[4-(4-Chlorophenylsulfonyl)benzoyl]-N 4-(aryl)-thiosemicarbazides and Products of Their Cyclization

In the present study, new 1,2,4-triazoles, 1,3,4-thiadiazoles, and acylthiosemicarbaz-ides derived from 4-(4-chlorophenylsulfonyl)benzoic acid hydrazide were synthesized and screened for their antimicrobial and analgesic activities. Acylthiosemicarbazides 2–4 were synthesized by a reaction of 4-(4-chlorophenyl-sulfonyl)benzoic acid hydrazide 1 with different arylisothiocyanates.4,5-Disubstituted-2,4-dihydro-3H-1,2,4-triazol-3-thiones 5–7 and 2,5-disubstituted-1,3,4-thiadiazoles 8–10 were obtained by dehydrative cyclization of corresponding acylthiosemicarbazide derivatives 2–4 in basic media (8% aqueous sodium hydroxide) and in acidic media (sulfuric acid or phosphorous oxychloride), respectively. The structures of the newly synthesized compounds have been confirmed on the basis of elemental analysis and spectral studies (IR, 1H NMR, 13C NMR, MS). Their antimicrobial activities against some bacteria and yeasts were investigated. The analgesic activity of all compounds was performed with two pharmacological tests: the writhing test induced with acetic acid and hot-plate test. The results showed that triazole 7 had the best antimicrobial activity against Bacillus cereus. In the chemical stimulus test, triazoles 6 and 7 were the most active compounds whereas in the hot-plate test thiadiazoles 9 and 10 exhibited the highest analgesic activity.

Synthesis, antimicrobial and cytotoxic activity of new heterocyclic hybrids based on 2,5-dimethylpyrrole and pyrrole scaffolds

A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs, some derived triazoles, azetidinones, thiazolidinones, and pyrroles have been synthesized in good yields and structures of these compounds were established by IR, 1H NMR, 13C NMR, mass spectral, and elemental analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis H37 Rv strain by the broth dilution assay method. Twenty one of these compounds displayed good antimicrobial activity, with a MIC value of 1-4 μg/ml. Several compounds 4c, 8-10, 15b-15h, and 16b-16d exhibited good in vitro antitubercular activity with MIC value 1-2 μg/ml. Further, some title compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines and A549 (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit antitubercular activity at non-cytotoxic concentrations.

Synthesis, spectral and thermal studies of some polymeric mixed ligand uracil–hydrazide complexes with transition metal ions

Polymeric mixed ligand complexes of the type [MCl(ur)(Bh)(H2O)] n and [M(ur)(Inh)(H2O)2] n , where, M = Co(II), Ni(II), Cu(II) and Zn(II), UR = uracil, Bh = benzoic acid hydrazide and Inh = isonicotinic acid hydrazide, have been prepared and characterized by elemental analyses, magnetic susceptibility measurements, thermo grams (TGA) studies, electronic, IR and ESR spectral studies. The magnetic moments and electronic spectral studies indicate high spin 6-coordinate octahedral geometry for all the complexes. ESR spectral studies on copper(II) complexes in solid state show a tetragonal octahedral environment around the metal ion and as the ground state. IR studies suggest that uracil behaves as monobasic bidentate ligand bonding through N(1) and C(4)=O groups to different metal atoms forming a polymeric framework. The ligand Bh bonds to metal through –NH2 and >C=O groups while Inh through –NH2 and a deprotonated C–O− groups. TGA studies of some of the complexes show multi-step decomposition pattern of their organic frameworks.

Synthesis and Biological Evaluation of Some Novel 5-[(3-Aralkyl Amido/Imidoalkyl) Phenyl]-1,2,4-Triazolo[3,4-b]-1,3,4-Thiadiazines as Antiviral Agents

A series of novel 4-amino-5-mercapto-3-[(3-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazoles (5a-d) were obtained by treating m-(aralkyl amido/imidoalkyl) benzoic acid hydrazides (3a-d) with carbon disulphide in alcoholic KOH and hydrazine hydrate, respectively. These triazole derivatives were employed in the synthesis of 5-[(3′-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (6a-d). The newly synthesized compounds were evaluated for their antiviral activity against two animal viruses, namely, Japanese encephalitis virus (JEV) strain P20778 and herpes simplex virus-1 (HSV-1) strain 753166.

Synthesis of new 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs and some derived oxadiazole, triazole and pyrrole ring systems: a novel class of potential antibacterial, antifungal and antitubercular agents

A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs, some derived 1,3,4-oxadiazoles, 5-substituted-4-amino-1,2,4-triazolin-3-thione and 2,5-dimethyl pyrroles have been synthesized in good yields and structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass spectral and elemental analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal and antitubercular activities against Mycobacterium tuberculosis H37Rv strain by broth dilution assay method. Twelve of these compounds displayed good antimicrobial activity, with a minimum inhibitory concentration (MIC) values 1–4 μg mL−1. Several compounds 4, 8d, 9, 12c–d and 12f–h exhibited good in vitro antitubercular activity with MIC values 1–2 μg mL−1. Further, some title compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines and A549 (lung adenocarcinoma) cell lines using MTT assay method. The results reveal that these compounds exhibit antitubercular activity at non-cytotoxic concentrations. Synthesis, spectral studies and antibacterial, antifungal and antitubercular activities of a novel series of pyrrole derivatives are described

ChemInform Abstract: Four‐Component Reaction Between Trimethyl Phosphite, Aroyl Chlorides and Dialkyl Acetylenedicarboxylate with Benzoic Acid Hydrazide

Abstractas a simple and efficient route for the synthesis of functionalized pyrazoledicarboxylates (IV) (8 examples)