Acetohydrazide Derivatives Research Articles

Molecular docking, ADMET, synthesis and evaluation of new indomethacin hydrazide derivatives as antibacterial agents

Bacterial infections pose an ongoing challenge due to resistance developed by infectious bacteria. So much research targeting designing new antibacterials is published annually. Our goal is to synthesize compounds that have given antibacterial activity according to molecular docking against the chosen target protein and that have acceptable ADMET properties that can be synthesized and used in the future. New 2-(5-methoxy-1-(4-chlorobenzene)-2-methyl-1H-indol-3-yl)acetohydrazide derivatives’ antibacterial efficacy against two common strains of Gram-negative and Gram-positive microorganisms has been developed, produced, and investigated. Sophisticated, modern analytical methods, including ATR-FTIR and 1H NMR spectroscopy, were used to determine their spectral and physicochemical features. Compound YA3N is more effective than ciprofloxacin against K. pneumonia (MIC = 125 µg/mL) and shows good suppression of isolated tests of E. coli (MIC = 125 µg/mL). While compound YA4C demonstrated comparable suppression of S. pyogenes strains (MIC = 250 µg/mL), compounds YA3S and YA4B exhibit lesser activity towards the tested strain of bacteria.

Anticholinesterase activities of novel isoindolin-1,3-dione-based acetohydrazide derivatives: design, synthesis, biological evaluation, molecular dynamic study

In pursuit of developing novel cholinesterase (ChE) inhibitors through molecular hybridization theory, a novel series of isoindolin-1,3-dione-based acetohydrazides (compounds 8a–h) was designed, synthesized, and evaluated as possible acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. In vitro results revealed IC50 values ranging from 0.11 ± 0.05 to 0.86 ± 0.02 µM against AChE and 5.7 ± 0.2 to 30.2 ± 2.8 µM against BChE. A kinetic study was conducted on the most potent compound, 8a, to ascertain its mode of inhibition, revealing its competitive mode against AChE. Furthermore, the binding interaction modes of the most active compound within the AChE active site was elucidated. Molecular dynamics simulations of compound 8a were performed to assess the stability of the 8a-AChE complex. In silico pharmacokinetic predictions for the most potent compounds indicated their potential as promising lead structure for the development of new anti-Alzheimer’s disease (anti-AD) agents.

Virtual Screening, ADMET Analysis, and Synthesis of 2-(1H-benzotriazol- 1-yl) N- substituted Acetohydrazide that Binds to the Glycoprotein B of Herpes Simplex Virus-I (HSV-I)

Background: Herpes simplex Virus type 1 (HSV-1) is a contagious human pathogen causing severe infection. In recent decades, the virus has become dormant and resistant to available treatment creating the need for the development of new therapeutic agents against it. Benzotriazole is a versatile molecule with a wide range of activities like antibacterial, antiprotozoal, antiulcer, anthelmintic, and antiproliferative activity. Methods: A series of 2-(1H- benzotriazole-1-yl) N- substituted acetohydrazide derivatives were synthesized using the method given in the literature. The derivatives were obtained in good yield and characterized by spectral methods of analysis. The antiviral activity against the glycoprotein B of Herpes Simplex Virus-I (HSV-I) was determined using molecular docking (2GUM). Result: All compounds had strong binding affinity over the standard Acyclovir. Compound 5h had the highest binding affinity and the highest inhibitory activity. Conclusion: The Benzotriazole-N- substituted acetohydrazide derivatives has the highest bind-ing affinity and good inhibition of glycoprotein B of Herpes Simplex Virus-I (HSV-I), which makes it a good antiviral agent.

Synthesis and Characterization of Pyridine Acetohydrazide Derivative for Antimicrobial Cotton Fabric

An increase in textile resistance to antimicrobial agents has posed a pressing need for the development of new antimicrobials. Therefore, the antimicrobial characteristics of thiophene and pyridine acetohydrazide derivatives have been developed as novel textile-modified complexes exhibiting antibacterial agents. Synthesis and characterization of pyridyl-thienyl acetohydrazide derivative (AHZ) using NMR (13C and 1H) and FTIR. Modification of cotton fabric (CF) with acetohydrazide (AHZ) and metal chlorides of divalent Cr, Mn, Co, Ni, Cu, and Zn and trivalent Fe, and Cr. SEM-EDX and Fourier-transform infrared were utilized to characterize cellulose-based cotton fabric (CF) attached to AHZ and their metal (M) complexes. Antimicrobial activity was examined against two types of bacteria, namely S. aureus and E. coli, and two types of fungi, namely C. albicans and A. flavus. All modified samples exhibited higher efficiency towards bacterial strains than fungal strains. In addition, cellulose modified with Ni (II) confers the most antibacterial protection efficiency.

Solvent free Synthesis of 2-[(5-methyl-1,3-benzoxazol-2-yl)sulfanyl] Acetohydrazide Derivatives as Novel Antimicrobial and Antitumor Agents

In pursuit of designing novel chemical entities with antitumor and antimicrobial activities, 2-[(5-methyl-1,3-benzoxazol-2-yl)sulfanyl]acetohydrazidederivatives have been synthesized as a scaffold of a series of amine derivatives, these analogs were on reductive amination with solvent free condition. All the synthesized compounds were assessed for antibacterial, antifungal, and antitumor activities against standard strains. The compounds 3a, 3b and 3g showed highest degree of inhibition against A. flavus and compounds 3a, 3b, 3d and 3h Showed highest degree of inhibition against C. albicans, compounds 3a,3e and 3g has shown the encouraging antibacterial activityresults against E. coli and compounds 3a, 3b and 3h exhibited a promising activity against B. subtilis. Compounds 3a, 3b and 3c exhibited promising antitumor activity.

Discovering phenoxy acetohydrazide derivatives as urease inhibitors and molecular docking studies

Helicobacter pylori causes severe stomach disorders and the use of enzyme inhibitors for treatment is one of the possible therapies. The great biological potential of imine analogs as urease inhibitors has been the focus of researchers in past years. In this regard, we have synthesized twenty-one derivatives of dichlorophenyl hydrazide. These compounds were characterized by different spectroscopic techniques i.e. NMR and HREI-MS. Compounds 2 and 10 were found to be the most active in the series. Structure-activity relationship has been established for all compounds based on different substituents attached to the phenyl ring that play a vital role in enzyme inhibition. From the structure-activity relationship, it has been observed that these analogs showed excellent potential for urease and can be an alternate therapy in the future. The molecular docking study was performed to further explore the binding interactions of synthesized analogs with enzyme active sites. Communicated by Ramaswamy H. Sarma

Third-order nonlinear response of a novel organic acetohydrazide derivative: Experimental and theoretical approach

A novel nonlinear optical (NLO) organic material of N'-[(E)-(5-bromofuran-2-yl)methylidene]-2-(6-chloropyridin-3-yl)acetohydrazide (BCA) was synthesized by reflux method. The synthesized material was characterized using various analytical techniques, including spectroscopic methods (NMR, FTIR, PXRD). The UV–Vis absorption spectrum of BCA was recorded in different solvents. A strong absorption peak was observed in the 280–350 nm range, indicating its potential for UV-based optoelectronic applications. BCA shows good NLO responses (αCT, βCT, γCTvalues) with different solvents. The dielectric measurements were performed using impedance spectroscopy with varying temperatures as a function of frequency. Thermal stability of the material was evaluated using thermogravimetric analysis, indicating high thermal stability up to 153.28°C. The FMO, MEP, and NBO analyses were implemented using density functional theory (DFT) calculations to investigate the BCA molecule's electronic structure and charge distribution. The topology studies were carried out using the QTAIM and NCI to understand the structure's chemical bonding and intermolecular interactions and the structure's chemical bonding and intermolecular interactions. NLO properties of the BCA material were investigated using the Z-scan technique with a continuous wave (CW) laser, revealing a strong third-order nonlinear susceptibility (χ(3)) value of 2.44 × 10−6 e.s.u. and potential optical limiting behavior (OL threshold = 3.437 × 103 Wcm−2). The TD-HF method performed the calculated molecular static and dynamic of NLO parameters with frequency. The computed γ value of 6.2 × 10−36 e.s.u. was found to be consistent with the experimental value. The results of this study recommend that the synthesized hydrazide derivative material has potential NLO applications.

Anti-Alzheimer activity of new coumarin-based derivatives targeting acetylcholinesterase inhibition.

New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 μM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.

Sulindac acetohydrazide derivative attenuates against cisplatin induced organ damage by modulation of antioxidant and inflammatory signaling pathways

This study aimed to explore the mechanisms of action of a sulindac acetohydrazide derivative, N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide, against anticancer drug cisplatin induced organ damage. Using a rodent model, various markers of organ function and signaling pathways were examined and validated by molecular docking studies. The study involves five groups of animals: control, DMSO, CDDP, CDDP + DMFM, and DMFM. Biochemical enzyme activity, histopathology, tissue antioxidant, and oxidative stress markers were examined. RT-PCR and western blot analyses were conducted for the expression of inducible cyclooxygenase enzyme (COX-2), nuclear factor kappa beta (NF-κB), p65, IL-1, TNF-α, and inducible nitric oxide synthase (iNOS). Flow cytometry analysis of CD4 + TNF-α, CD4 + COX-2, and CD4 + STAT-3 cells in whole blood was performed. Structural and dynamic behavior of DMFM upon binding with receptor molecule molecular docking and dynamic simulations were performed using bioinformatics tools and software. Treatment with DMFM reversed cisplatin-induced malondialdehyde (MDA) and nitric oxide (NO) induction, whereas the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) in the kidney, heart, liver, and brain tissues were increased. DMFM administration normalized plasma levels of biochemical enzymes. We observed a marked decline in CD4 + STAT3, TNF-α, and COX2 cell populations in whole blood after treatment with DMFM. DMFM downregulated the expression factors related to inflammation at the mRNA and protein levels, i.e., IL-1, TNF-α, iNOS, NF-κB, STAT-3, and COX-2. Dynamic simulations and in silico docking data supports the experimental findings. Our experimental and in silico results illustrated that DMFM may affect protective action against cisplatin-induced brain, heart, liver, and kidney damage via reduction of inflammation and ROS.

Experimental and computational evidence for stabilising parallel, offset π[C(O)N(H)NC]⋯π(phenyl) interactions in acetohydrazide derivatives

Stabilising π[C(O)N(H)NC]⋯π(phenyl) interactions are described.

Design, Synthesis, Anti-inflammatory & Anticonvulsant Activity of Substituted Heterocyclic Compounds

Aim: To design, synthesize, anti-inflammatory & anticonvulsant activity of substituted coumarin acetohydrazide derivatives.
 Study Design: Experimental work related to Anti-inflammatory & Anticonvulsant activity.
 Methodology: Coumarin acetohydrazide derivatives were synthesized by reacting substituted isatin with 7-hydroxy-4-methyl-coumarin in glacial acetic acid to determine their anti-inflammatory & anticonvulsant activities. Molecular docking study was performed against the COX enzyme for anti-inflammatory activity & carbonic anhydrase II enzyme for anticonvulsant activity. Anti-inflammatory activity was done by carrageenan induced paw edema method in rats at a dose of 200 mg/kg body weight. Anticonvulsant activity was studied in rats at a dose of 200 mg/kg body weight; in the maximal electroshock (MES) induced seizures model.
 Results: (Z)-2-(4,8-dimethyl-2-oxo-2H-chromen-7-yl)oxy)-N-(5-nitro-2-oxoindolin-3-ylidine) aceto-hydrazide and (Z)-2-(4-methyl-2-oxo-2H-chromen-7yl) oxy)-N-(1-methyl-2-oxoindolin-3-ylidene) acetohydrazide showed the highest anti-inflammatory activity as compared to Celecoxib after 5 h with 71.94 to 77.96 % inhibition. Most of the compounds displayed anticonvulsant activity in the MES screen at a dose 200 mg/kg. Out of twelve compounds (Z)-N-(5-chloro-2-oxoindolin-3-ylidene)-2-((4-methyl-2-oxo-2H-chromen-7-yl) oxy) acetohydrazide and (Z)-2-((4-methyl-2-oxo-2H-chromen-7yl) oxy)-N-(1-methyl-2-oxoindolin-3-ylidene) acetohydrazide shown most significant activity with remarkable protection (67%) against MES induced convulsions. The structure-activity relationship concluded valuable pharmacophoric information, that the substitution on isatin ring has a significant effect on preventing inflammation & the seizure formation.
 Conclusion: From the molecular docking study & biological activity determines that all synthesized coumarin acetohydrazide derivatives shows anti-inflammatory activity as compared to Celecoxib & anticonvulsant activity as compared to Phenytoin.

Design, Synthesis and Antibacterial, Antifungal Activity of Some Coumarin Acetohydrazide Derivatives

We have designed and synthesized (Z)-2-(5-methyl-2-oxo-2H-chromen-7-yl) oxy)-N’-(2-oxoindolin-3-ylidin) acetohydrazide derivatives by reacting 7-hydroxy-4-methyl-coumarin and substituted isatin to afford 12 substituted coumarin acetohydrazide derivatives. The synthesized compounds of coumarin acetohydrazide derivatives were designed and evaluated to study for their possible interactions as DNA gyrase inhibitors. All the synthesized coumarin acetohydrazide compounds have been characterized by spectral analysis IR, 1H NMR and mass spectroscopy. The compounds have been evaluated for In vitro antibacterial and antifungal activity against S. aureus, B. subtilus, E. coli, P. aeruginosa and fungi C. albicans and A. niger. In case of Gram positive bacteria and Gram negative bacteria Compound P5C, M5C, C5C exhibited significant activity. Compounds P5N, M5N, C5N shown moderate activity. Compound P5C, M5C, C5C shown significant Antifungal activity against C. albicans and A. niger. Compounds P5C, M5C, C5C are found to exert significant antibacterial as well as antifungal activity and can serve as potential compound against infectious diseases in future.

Synthesis, antimicrobial, antioxidant, and ADMET studies of quinoline derivatives

The synthesis, antimicrobial, and antioxidant activities of new quinoline analogs were carried out with the aim to find possible hits/leads that can be taken up for future drug development. A series of 2-amino-N’-((2-chloroquinolin-3-yl)methylene)acetohydrazide derivatives (6a-h) have been synthesized by reacting 2-chloro-N’-((2-chloroquinolin-3-yl)methylene)acetohydrazide (5a) and N’-((6-bromo-2-chloroquinolin-3-yl)methylene)-2-chloroacetohydrazide (5b) with secondary amines (Morpholine, diethylamine, piperidine and 1-methylpiperazine). The characterization was achieved by FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. The in silico ADMET studies of the synthesized molecules were analyzed for their drug likeliness and toxic properties. The ADMET study indicates that the synthesized compounds were found to be possessing reliable ADME properties and are nontoxic. The antimicrobial properties were tested against bacterial and fungal species with amoxicillin and fluconazole as standard drugs. The compounds 6a, 6c, 6e, and 6g exhibited good antibacterial potency against P. aeruginosa, and the compounds 6a, 6f, and 6h have shown good activity against E. coli with 1000 µg/mL. The compounds 6b, 6c, and 6e have moderate activity against fungal species C. oxysporum and the compounds 6c, 6e, 6f, 6g, and 6h have good activity against P. chrysogenum. Synthesized compounds were also tested for the DPPH· free radical scavenging activity to check the antioxidant potential, and the results revealed that the compounds 6a, 6b, 6c, and 6e have exhibited antioxidant potency than the remaining synthesized derivatives. The possible hits generated from biological activity could be taken for the generation of lead molecules for the drug discovery of antimicrobial and antioxidant entities from quinoline.

Synthesis and physical-chemical properties of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives and their evaluation for antimicrobial and diuretic activities

One of the most important tasks of our indigenous pharmaceutical science is the necessity for new medicines because existing drugs are characterized by various side effects, resistance, high toxicity, and so on. New bioactive molecule synthesis utilizes substances of natural origin as well as chemically modified ones. Thus, the researcher’s attention is mainly focused on 3-,7-,8-substituted derivatives of the natural heterocyclic xanthine system, which possess a wide range of pharmacological action. Synthesis of a novel of (3-benzyl-8-propylxanthin-7-yl)acetohydrazides with antimicrobial and diuretic activities described in the paper.
 The aim of this work is to develop efficient methods for synthesis of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives, and to study their physical-chemical properties.
 Materials and methods. Two-hour boiling of propyl 2-(3-benzyl-8-propylxanthine-7-yl)acetate by excess hydrazine hydrate in propan-2-ol medium have yielded the key the key intermediate 2-(3-benzyl-8-propylxanthine-7-yl)acetohydrazide. Further transformation of the latter has led to formation of corresponding acetohydrazide derivatives achieved by the reaction with aliphatic, aromatic, heterocyclic aldehydes, and ketones. The structure and the relative configuration of the synthesized compounds were elucidated by analyzing their physical-chemical data.
 Results. The synthesis and optimization of reaction conditions of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives were conducted. The identification of all synthesized compounds was aided by various physical-chemical methods (thin layer chromatography, elemental analysis, IR, and 1H NMR spectroscopy).
 Conclusions. As a result of synthetic research the preparative synthesis method of (3-benzyl-8-propylxanthin-7-yl)acetohydrazide derivatives possessing antimicrobic, and diuretic activities was developed.

Synthesis and biological activity of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives.

The synthesis and antimicrobial evaluation of new 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives was investigated. According to the literature, there are a lot of antimicrobial agents among the pyrimidines and hydrazides, and therefore it seems promising to use 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide as a base object for synthesizing new biologically active substances. 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide was obtained by the hydrazinolysis of ethyl thioacetate, using a 3-fold molar excess of 85 % hydrazine hydrate in ethanol, at room temperature. Interaction of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide with ketones during boiling in ethanol yielded N-ylidenehydrazides. The solid obtained by concentration was collected, and then purified by recrystallization. The new compounds were characterized by 1H, 13C NMR, IR spectroscopy and elemental analysis. The antibacterial and antifungal activities of the new compounds were analysed using agar diffusion and tenfold broth (pH 7.2 – 7.4) dilution methods, in comparison with the clinical used drugs, ceftriaxone and Pimafucin. The structure–activity studies showed that, depending on the nature of the hydrazide fragment, the newly synthesized compounds exhibited varying degrees of microbial inhibition. Within the same series the antimicrobial activity depends on the nature of the substituent attached to the benzene ring. The investigation of antibacterial screening data revealed that the compounds N′-[1-(4-aminophenyl)ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, N′-[1-(4-hydroxyphenyl)ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, N′-[1- (2,5-dihydroxyphenyl) ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)-pyrimidin-2-ylthio]acetohydrazide were found to be more potent than the other synthesized analogues.

Microwave assisted synthesis of N-substituted benzylidene-2-(1H-benzotriazol-1-yl) acetohydrazide derivatives as antibacterial agents

Microwave assisted synthesis of N-substituted benzylidene-2-(1H-benzotriazol-1-yl) acetohydrazide derivatives as antibacterial agents

Non-covalent interactions abetted supramolecular arrangements of N-Substituted benzylidene acetohydrazide to direct its solid-state network

Intra-molecular hydrogen bond modulation of compounds positively impacts their solubility, permeability and as well as potency in the field of medicinal chemistry. Herein, N-substituted benzylidene acetohydrazide derivative: (Z)-2-((6-chloropyridin-2-yl)oxy)-N'-(2-hydroxy-3-methoxybenzylidene)acetohydrazide (HOBAH), a novel solid state network was synthesized efficiently via sono-chemical approach. The structural characterization of HOBAH was achieved by single crystal analysis which exposed intra-molecular NH…O, OH…N bonding and intermolecular NH…O, OH…O and comparatively weak CH…O hydrogen bonding being responsible for the crystal packing. Theoretical calculations by applying the density functional theory (DFT) at DFT/B3LYP/6–311G(d,p) were completed. The characteristic of HOBAH was evaluated from a relaxed PES scan analysis and the HOBAH conformations with minimum energy have been identified. Hirshfeld surface (HS) and the quantum theory of atoms in molecules (QT-AIM) analyses bolstered in quantifying the existing non-covalent interactions. QT-AIM analysis unveiled that strong NH…O-H and CO…H-O hydrogen bonds (HBs) and other van der Waals interactions were responsible for the stabilization of these solid state networks. All non-covalent interactions with positive laplacian of electron density (∇2ρ) values from QT-AIM analysis corroborated well with the internal charge transfer and the hyper-conjugative interactions explored by NBO analysis. Moreover, all significant results were endorsed by both NPA and FMO evaluations. FMO analysis later assisted in the calculation of global reactivity indices. However, local reactivity indices were computed with Fukui function calculations. Lastly, molecular electrostatic potential (MEP) was plotted which confirmed the nucleophilic and electrophilic sites of HOBAH as elaborated by the reactivity indices.

Design, synthesis, in silico, and in vitro evaluation of 3-phenylpyrazole acetamide derivatives as antimycobacterial agents.

Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are efficient and can reduce the duration of therapy against drug-resistant strains, are an urgent unmet need of the hour. In our current study, a series of new 2-(3-phenyl-1H-pyrazol-1-yl)acetamide and N'-benzylidene-2-(3-phenyl-1H-pyrazol-1-yl)acetohydrazide derivatives were designed, synthesized, and evaluated for their antimycobacterial potential. The biological evaluation revealed that 6b, 6m, 6l, 7a, and 7k exhibited selective and potent inhibitory activity against Mtb. Furthermore, compounds 6m and 7h were found to be nontoxic to Vero cells with CC50 of greater than20and 80 mg/ml, respectively, and exhibited promising selectivity indices (SI) of greater than666 and320, respectively. All derivatives exhibited excellent ADME (absorption, distribution, metabolism, and excretion) properties in silico. Also, all the derivatives were found compliant with Lipinski's rule of five, showing their druggability profile. Molecular docking insights of these derivatives have shown outstanding binding energies on the mycobacterial membrane protein largetransporters. These results indicate that this scaffold may lead to a potential antimycobacterial drug candidate in the discovery of antitubercular agents.

Synthesis of Novel Diclofenac Hydrazones: Molecular Docking, Anti-Inflammatory, Analgesic, and Ulcerogenic Activity

This study was aimed to design novel diclofenac hydrazones having anti-inflammatory and analgesic activity with gastric sparing effect. A new series of 2-[2-(2,6-dichloroanilino)phenyl]-N’-[(substituted phenyl) methylidene] acetohydrazide derivatives (1−14) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity. The compounds were identified and confirmed by elemental analysis and spectral data. During anti-inflammatory activity by carrageenan-induced paw edema method, compounds (2, 3, 7, 8, 11, and 13) were found to be most promising. Compounds 3, 8, and 13 have been found to have significant analgesic activity compared to the reference drug diclofenac in analgesic activity by both the hot plate method and acetic acid-induced writhing method. The compounds which presented highly significant anti-inflammatory and analgesic activity were further tested for their ulcerogenic activity. Compounds 3 and 8 showed maximum ulcerogenic reduction activities. Compound 8 was found to have LD50 of 168 mg/kg. Compound 8 with 3,5-dimethoxy-4-hydroxyphenyl substitution was found to be the most promising anti-inflammatory and analgesic agent with gastric sparing activity. Molecular docking of compounds was performed for COX−1/COX−2 binding site. Lead compound 8 showed better binding affinities of −9.4 kJ/mol with both COX-1 and COX-2 as compared to the standard drug, diclofenac with binding affinities of −6.6 kJ/mol and −8.1 kJ/mol for COX−1 and COX−2, respectively.

Evaluation of the Antioxidant Activity of Some Imines Containing 1H-Benzimidazoles.

The in vitro antioxidant properties of some 2-(2-phenyl)-1H-benzo(d)imidazol-1-yl)-N'-(arylmethylene) acetohydrazide derivatives (1-12) were investigated in this study. The in vitro antioxidant activity of compounds 1-12 was explored by determination of rat liver microsomal nicotinamideadenine dinucleotide phosphate dependent inhibition on lipid peroxidation (LPO) levels and microsomal ethoxyresorufin O-deethylase (EROD) activity. All synthesised compounds had LPO inhibitory activity (15-57%) except compound 6, which contains a thiophene ring. Almost all the compounds displayed slightly inhibitory activity (2-20%) on EROD. The most active compound, 3 bearing a p-bromophenyl substituent at the second position of the benzimidazole ring, caused 57% inhibition of LPO level, while butylated hydroxytoluene showed 65% inhibition. None of the synthesised compounds had a marked inhibitory effect on EROD activity.