Acyl Hydrazone Research Articles

Investigating the Antiproliferative Activity of Novel 4-Chloro-8-Nitro-1,2-Dihydro-3-Quinoline Acylhydrazones on Human Cervical Cancer Cell Lines.

A new series of acyl hydrazones have been synthesized from 4-chloro-8-nitro-1,2-dihydroquinoline-3-carbaldehyde. These compounds were characterized using various spectroscopic techniques. Density functional theoretical (DFT) studies were conducted to understand the correlation between electronic parameters and biological activity. The biological activity of the compounds was theoretically examined through molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis. The compounds demonstrated high absorption rates and were found to be non-hepatotoxic. Preliminary cytotoxicity screenings against HeLa cell lines identified compound 7 as the most potent, with an IC50 value of 18.8 μM. This compound was further selected for bioimaging studies. The results indicate that compound 7 induces apoptosis at its IC50 concentration, suggesting its potential as an anticancer agent.

Acyl hydrazone derivatives with trifluoromethylpyridine as potential agrochemical for controlling plant diseases.

Crops are consistently under siege by a multitude of pathogens. These pathogenic microorganisms, including viruses and bacteria, result in substantial reductions in quality and yield globally by inducing detrimental crop diseases, thus posing a significant challenge to global food security. However, the biological activity sepectrumof commercially available pesticides is limitedand the pesticide efficacy is poor, necessitating the urgent development of broad-spectrum and efficient strategies for crop disease prevention and control. The bioassay results revealed that certain target compounds demonstrated outstanding in vivo antiviral efficacy against cucumber mosaic virus and tobacco mosaic virus. In particular, compound D6 showed remarkable antiviral activity against CMV, significantly higher than that of the control agent ningnanmycin. Mechanism of action studies have shown that compound D6 could enhance the activity of defense enzymes and upregulate the expression of genes related to disease resistance, thereby enhancing the antiviral effects in plants. In addition, these compounds displayed superior inhibitory activity against plant bacterial diseases. For Xoo, compound D10 showed an excellent inhibitory effect that was better than that of the control agent bismerthiazol. Scanning electron microscopy and fluorescence double-staining experiments revealed that compound D10 effectively inhibited bacterial growth by disrupting the cell membrane. A series of trifluoromethyl hydrazone derivatives were designed and synthesized, and it was found that they have control effects on plant viruses and bacterial diseases. In addition, this study revealed the mechanism of action of the active compounds and demonstrated their potential as multifunctional crop protectants. © 2024 Society of Chemical Industry.

Organo Mediated Sustainable Synthesis and In‐Silico Studies of Novel Benzisoxazole‐Chromene Acyl Hydrazones as AChE Inhibitors

AbstractA new class of benzisoxazole‐Chromene (BC) analogues containing acyl hydrazones BCA (5a‐5m) were obtained by the condensation of different benzo hydrazides with BCs in good yield. All the synthesized BCA analogues were evaluated for their in‐silico activity against Acetylcholine Esterase (AChE). According to docking experiments, the co‐crystallized ligand was outperformed by derivatives 5e (4‐benzisoxazole‐chromene‐3‐(4hydroxyphenyl) acrylohydrazide), 5m (7‐chloro,4‐hydroxy) and 5l (8‐methyl, m‐nitro) showed superior binding modes and binding free energies whereas compound 5j (8‐methyl, 4‐hydroxy) showed appropriate binding energy. These moieties containing acyl hydrazone has shown 4‐fold increase in the binding interactions and orientation. According to ADMET and toxicity studies, derivatives 5e, 5m, 5j, and 5l had the potential to be drugs and have proven to be safe when evaluated using seven toxicity models. Further on checking selectivity with the other cholinesterase enzyme, 5l came out to be selective towards AChE whereas 5e & 5j were acting on another target as well. Finally, DFT analysis validated the binding of the derivatives towards AChE and moreover Molecular Dynamic investigation revealed that 5l is the most capable candidate to interact with the target receptor by comparing its molecular orbital energies, molecular electrostatic potential maps, and ligand movement against the co‐crystallized Ligand.

Acyl hydrazone‐based supramolecular polymer for ultrasensitive detection of Fe3+, Pd2+, H2PO4− and its application for Suzuki coupling reactions

A novel acylhydrazide‐based gelator (BE) was successfully built without the use of traditional fluorescent groups. Surprisingly, in 1,2‐propanediol, the BE can further self‐assemble into a stable supramolecular gel (OBE) and display significant blue‐white aggregation‐induced enhanced emission (AIEE). Interestingly, based on the excellent coordination capacity of acyl hydrazone bonds, the OBE demonstrated a sensitive response to Pd2+ and Fe3+, with corresponding lowest limits of detection of 21.8 and 37.3 ppb, respectively. More interesting, H2PO4− could only be constantly recognized by the Pd‐OBE (Pd2+ coordinated with OBE). Fourier transform infrared (FT‐IR), scanning electron microscopy (SEM), X‐ray diffraction (XRD), density functional theory (DFT) and rheological measurements, the self‐assembly process of OBE, and the ion recognition sensing mechanism were extensively examined. Moreover, xerogel OBE as supporter, a novel heterogeneous catalyst Pd/OBE is prepared. The catalyst displays outstanding activity and stability for Suzuki coupling reactions in water. It can be easily reused for at least five runs with no decrease in the catalytic activity.

Abstract PO3-26-09: A novel class of RNR inhibitors that induces genomic instability and breast cancer cell death without inducing overt toxicities

Abstract Despite the development of screening techniques and therapies, nearly 30% of breast cancers progress to Stage IV metastatic disease. These advanced cancers are highly proliferative, engaging in ongoing DNA synthesis that requires ribonucleotide reductase (RNR), the rate-limiting enzyme for dNTP synthesis. RRM2, the small subunit of RNR, activates the enzyme, increases deoxynucleotide pools, and is overexpressed in many cancers, including breast cancer. Thus, RNR is an established therapeutic target in advanced breast cancer. Currently, gemcitabine is the only FDA-approved RNR inhibitor used to treat Stage IV disease. As a nucleoside analog, gemcitabine also causes severe dose-limiting toxicities (i.e. myelosuppression and hepatotoxicity) due to off-target DNA replication termination. We hypothesize that a novel, non-nucleoside, RNR inhibitor may overcome these limitations. To address this, we developed TMU27a, a derivative of naphthyl salicylic acyl hydrazone (NSAH), which was identified in an in silico screen for its high-affinity binding to the RNR catalytic site. To measure direct interactions between TMU27a and purified RNR protein, we used surface plasmon resonance, revealing on-target, tight binding (Kd = 150 nM). Unbiased docking and molecular dynamics simulations (using lowest energy calculations) predicted the binding sight of TMU27a to be the catalytic site of RNR, where it is stabilized through extensive interactions formed with conserved residues. Preliminary docking predictions also indicate multiple clash sites between TMU27a and the DNA polymerase lambda nucleotide pocket even in the lowest energy pose (unlike gemcitabine), suggesting that TMU27a inhibits RNR activity through a novel mechanism without significant off-target binding to other nucleotide binding proteins that contribute to toxicity. Demonstrating on-target inhibition, TMU27a reduces dATP levels and induces S and G2/M-phase stalling, leading to significant DNA damage and chromosomal instability. This excessive genomic damage causes growth repression, apoptosis, and senescence in several triple negative breast cancer (TNBC) cell lines. In xenograft mouse models of TNBC, TMU27a fully suppressed tumor growth without impacting mouse weight, suggesting strong drug efficacy in the absence of overt toxicity. Moreover, while short-term exposure to gemcitabine suppresses red and white blood cell populations, TMU27a does not. Together, these data indicate that TMU27a and its potential analogs are novel, non-toxic RNR inhibitors that overcome the limitations of gemcitabine for treating breast cancer. We are currently investigating how and where TMU27a binds human RNR using cryo-electron microscopy with the goal of generating a novel class of RNR inhibitors through structure-based drug design, improving binding affinity and selectivity. Citation Format: Taylor Baker, Kristen Weber-Bonk, Wei Huang, Derek Taylor, Ruth Keri. A novel class of RNR inhibitors that induces genomic instability and breast cancer cell death without inducing overt toxicities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-26-09.

Ion pair induced supramolecular assembly for development of novel pyridine 2, 6 diamide spacer acyl hydrazone-based derivatives for selective sensing of ZnCl2 and AlCl3

The work reports the development of a novel pyridine 2, 6 diamide spacer acyl hydrazone-based dual sensor H2L via two intermediates 1 and 2. The sensor as well as intermediates have been spectroscopically characterized. The structure of intermediate 1 is validated by its single crystal data analysis. As H2L bears both amide and acyl hydrazone moiety which have selective detection ability of anion and cation respectively, after rigorous characterization, the sensors are exposed to check their dual binding behavior. The results of several spectroscopic studies disclose the fact that H2L can optically and fluorometrically detect Al (III) and Zn (II) among several competitive cations and Cl− among competitive anions in semi-aqueous and aqueous medium respectively. Interestingly in a 9:1 DMSO-water medium, the probe can act as an ion pair sensor and in this medium, the probe can simultaneously detect Zn (II)/Cl- and Al (III)/Cl- forming H2L-ZnCl2, H2L-AlCl3 adduct. The 1:1 probe-analyte ion-pair binding is confirmed by NMR and mass spectral study. The Density Functional Theory (DFT) study optimizes the structures of the probe-analyte complexes. Impressively the probe has the potential to detect and quantify the Al (III) from market-available drug samples.

A novel chromene acyl hydrazone Schiff base organogel with colorimetric Cu2+ responsive

A novel chromene acyl hydrazone Schiff base organogel with colorimetric Cu2+ responsive

Synthesis of Acyl Hydrazides and Hydrazones from Activated Amides

AbstractAcyl hydrazide and acyl hydrazone synthesis methods were developed. They involve the reaction of an activated amide with hydrazine under transition-metal-catalyst-free conditions. Additionally, acyl hydrazones were synthesized by extending the same reaction procedure in the presence of aldehydes (or ketones). These reactions were performed in an aqueous environment at 25 °C, demonstrating the successful attainment of the desired compounds with high yields.

Crosslinking through acyl hydrazone formation by reacting water soluble polyurethanes derived from ketone diol comonomers and those containing hydrazide pendant groups

Fully water-based formulations are gaining traction with the sustainability initiative for various applications. In this regard, producing the components required for making these formulations by eliminating toxic reagents is highly desirable. Hydrazone formation is widely used as a non-hazardous curing process in coating applications. Generally, carbonyl compounds that are used in the hydrazone forming reaction are nearly exclusively derived from vinyl polymers. This article describes a facile process for making carbonyl group containing diols and keto group containing water-soluble polymers therefrom by step growth or condensation polymerization. A water-soluble polymeric hydrazide was prepared by DCC coupling reaction between hydrazine hydrate and a polyurethane bearing pendant carboxylic acid group. The aqueous solutions of keto group containing, and hydrazide pendant polymers were mixed and coated on glass slides. Subsequently, the acyl hydrazone formation was studied under static heating in a hot air oven and a dynamic condition provided by blowing air under ambient conditions with a hair dryer. The dynamic nature of the latter process more than compensated the absence of direct heating to induce drying and hydrazone formation sequentially as studied by FT-IR spectroscopy. The cured slides were stable to water and were sensitive to weakly acidic aqueous solutions (about pH 3) formed by dissolving citric acid in water. The keto group containing diols enabled the hydrazone formation in polymer pairs entirely derived from step growth polymerization. As step growth or condensation polymers potentially offer both degradability and recycling through the cleavage of labile bonds prevailing in the polymer backbone, these keto group containing diols are preferable alternatives to keto group containing vinyl monomers commonly used for making hydrazones.

Synthesis, crystal structure,anti-tuberculosis activity and toxicity prediction of N-(4-bromophenyl)-3-(5-(4-chloro-3-nitrophenyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamide

Aminoacyl-tRNA synthetases are widely distributed in all organisms and plays an important role in the synthesis of proteins. Because of the significant differences between prokaryotic and eukaryotic aminoacyl tRNA synthetases, they become promising targets for effective anti-tuberculosis treatments. Previously, our research group designed and synthesized benzene sulfonamide compounds containing substituted acylhydrazones using molecular docking and fragment linking methods. Among them, compound 1A showed the highest activity, specifically targeting Mtb LeuRS, with an IC50 = 21.37 ± 0.2 μM and a MIC = 18.85 ± 0.2 μM for Mtb H37Ra. In order to solve the problem of excessive flexibility in this kind of compound, the conformation restriction strategy was adopted, and the acyl hydrazone structure was replaced by 1,3,4-oxadiazole ring to obtain D series of compounds. Compound D4 was characterized by single crystal X-ray diffraction. Compound D4 demonstrated an IC50 = 70.51 ± 0.2 μM against Mtb LeuRS and an MIC = 53.57 ± 0.2 μg/mL against Mtb H37Ra. In order to further understand the structural interaction between this series of compound and isoleucine, the crystal structure and related physical and chemical properties of compound D4 were comprehensively studied.

Co(II) acetateassisted direct synthesis of acyl hydrazones from acyl hydrazides under mild condition.

Acyl hydrazones are a class of synthetically important organic compounds that are recurrently in high demand for synthesis and use in various fields of chemistry and biology. We report the first Co(II) catalyzed one-component one-pot sustainable synthesis of acyl hydrazones only from acyl hydrazides under mild reaction conditions. Traditional and contemporary methodologies use two components (usually acyl hydrazides and aldehydes/ketones/alcohols/styrene) as the coupling partners. Our protocol, on the other hand, involves the in situ generation of aldehyde intermediate (detected by gas chromatography) from the acyl hydrazide, which then undergoes condensation with another molecule of the same acyl hydrazide in the same pot to yield acyl hydrazones in presence of mild base K2CO3 and low-cost Co(OAc)2·4H2O as catalyst. This method shows good functional group tolerance with good to excellent yield of products. Furthermore, some of the resulting acyl hydrazones have been used as synthetic precursors and explored in various post-synthetic modifications to afford N-heterocyclic compounds. Furthermore, photoswitchable properties of few synthesized acyl hydrazones are also explored using their E/Z isomerization around the C=N bond, as realized by high-pressure liquid chromatography (HPLC) and UV-vis spectroscopic studies.

Old Dogs with New Tricks: Antiparasitic Potential of Structurally Diverse 5-Nitrofuran and 5-Nitrothiophene Imines and Acyl Hydrazones

Miscellaneous imines and acyl hydrazones were prepared from 5-nitrofuraldehyde and 5-nitrothiophene-2-carboxaldehyde. Their activities against Toxoplasma gondii and Leishmania major parasites were evaluated. Promising antiparasitic effects and selectivities were observed for certain acyl hydrazones and imines. Cobalt(II) and copper(II) complexes conserved the high anti-Toxoplasma activities of 3-hydroxy-2-naphthoic carboxyl hydrazone (2a). In addition, sound activities against L. major promastigotes were observed for various analogs of 2a (2b and 2i) and pyrid-2-ylpyrazole-based imines (3g and 3h). Relatively low toxicities to kidney cells and macrophages indicate promising selectivity profiles for these compounds.

Pyrazole‐Imidazopyridine Hydrazones: Synthesis, α‐Glucosidase, α‐Amylase Inhibitory Activity and Computational Studies

AbstractDiabetic complications poses major threat to mankind which found to be dangerously fatal all over the world. It is thought vital to find new class of molecules to combat diabetic problems. Thus, in continuation of our efforts in identifying new class of α‐glucosidase and α‐amylase inhibitors, a novel series of hybrid molecules comprising of imidazo[1,2‐a]pyridine and pyrazoles, i. e. (3‐(Substituted phenyl)‐1H‐pyrazol‐4‐yl)methylene)‐2,7‐dimethyl‐1H‐imidazo[1,2‐a]pyridine‐3‐carbohydrazide derivatives (8 a–m) were designed through a acyl hydrazone bridge. The compound (Z)‐N′‐({3‐[4‐(2‐Fluorobenzyloxy)phenyl]‐1H‐pyrazol‐4‐yl}methylene)‐2,7‐dimethyl‐imidazo[1,2‐a]pyridine‐3‐carbohydrazide (8 m) emerged as potent inhibitor of α‐glucosidase and α‐amylase enzyme with IC50 5.00±0.10 μg/mL and 15±0.35 μg/mL respectively. The enzyme kinetics studies revealed reversible non‐competitive mode of inhibition of 8 m against both enzymes. In addition, these compounds were subjected to detailed in‐silico studies to understand their interaction with respective target proteins.

Novel salicylic acid derivatives connecting to five-membered cycle through an acyl hydrazone bond as multi-stimuli responsive fluorescent smart materials with photoswitching properties

In order to exploit novel multi-stimuli responsive fluorescent materials, a series of novel fluorescent molecules of salicylic acid derivatives were designed and synthesized via introducing pyrazole or cyclopentane to the salicylic acid scaffold through a special Schiff base–acylhydrazone, and the molecular structures of representative compounds A2 and A4 were verified via single crystal X–ray diffraction. All title molecules could exhibit obvious solvatofluorochromism from cyan to indigo in several solutions with different polarity. The fluorescence titration data exhibited compound A2 and complex A2-Cu2+ with prime detection limits to Cu2+ (0.24 μM) and S2- ions (2.83 μM). The sensitive recognition of A2 to trifluoroacetic (TFA) and A2-TFA to triethylamine (TEA) were also confirmed via fluorescent titration experiments in various solutions, respectively. What’s more, the 1H NMR and UV/Vis absorption spectra further explained the mechanism between molecules and ions or molecules and TFA/TEA. Besides, the photoswitching properties of the compounds A2 and A3 could be demonstrated via the irradiation of special wavelength light or heating accompanied with changes in quantum yields. In addition, these phenomena of multiple responses were explained via Density Functional Theory (DFT) based on the Gaussian calculations. Thus, this work provided a preliminary basis for the research of multi-stimuli responsive fluorescent molecules with photoswitching properties.

Acyl Hydrazides and Acyl Hydrazones as High-Performance Chemical Exchange Saturation Transfer MRI Contrast Agents.

Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0-4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8-5.0 ppm from water while exchange rates varied from ~680 to 2340 s-1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.

High-Performance Multi-Dynamic Bond Cross-Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene-Cell Combination Therapy of Intervertebral Disc Degeneration.

Chronic inflammatory diseases, such as intervertebral disc degeneration (IVDD), which affect the lives of hundreds of millions of people, still lack effective and precise treatments. In this study, a novel hydrogel system with many extraordinary properties is developed for gene-cell combination therapy of IVDD. Phenylboronic acid-modified G5 PAMAM (G5-PBA) is first synthesized, and therapeutic siRNA silencing the expression of P65 mixed with G5-PBA (siRNA@G5-PBA) is then embedded into the hydrogel (siRNA@G5-PBA@Gel) based on multi-dynamic bonds including acyl hydrazone bonds, imine linkage, π-π stacking, and hydrogen bonding interactions. Local and acidic inflammatory microenvironment-responsive gene-drug release can achieve spatiotemporal regulation of gene expression. In addition, gene-drug release from the hydrogel can be sustained for more than 28 days in vitro and in vivo, greatly inhibiting the secretion of inflammatory factors and the subsequent degeneration of nucleus pulposus (NP) cells induced by lipopolysaccharide (LPS). Through prolonged inhibition of the P65/NLRP3 signaling pathway, the siRNA@G5-PBA@Gel is verified to relieve inflammatory storms, which can significantly enhance the regeneration of IVD when combined with cell therapy. Overall, this study proposes an innovative system for gene-cell combination therapy and a precise and minimally invasive treatment method for IVD regeneration.

Study of the Metabolic Profiles of "Indazole-3-Carboxamide" and "Isatin Acyl Hydrazone" (OXIZID) Synthetic Cannabinoids in a Human Liver Microsome Model Using UHPLC-QE Orbitrap MS.

Unregulated core structures, "isatin acyl hydrazones" (OXIZIDs), have quietly appeared on the market since China legislated to ban seven general core scaffolds of synthetic cannabinoids (SCs). The fast evolution of SCs presents clinical and forensic toxicologists with challenges. Due to extensive metabolism, the parent compounds are barely detectable in urine. Therefore, studies on the metabolism of SCs are essential to facilitate their detection in biological matrices. The aim of the present study was to elucidate the metabolism of two cores, "indazole-3-carboxamide" (e.g., ADB-BUTINACA) and "isatin acyl hydrazone" (e.g., BZO-HEXOXIZID). The in vitro phase I and phase II metabolism of these six SCs was investigated by incubating 10 mg/mL pooled human liver microsomes with co-substrates for 3 h at 37 °C, and then analyzing the reaction mixture using ultrahigh-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. In total, 9 to 34 metabolites were detected for each SC, and the major biotransformations were hydroxylation, dihydrodiol formation (MDMB-4en-PINACA and BZO-4en-POXIZID), oxidative defluorination (5-fluoro BZO-POXIZID), hydrogenation, hydrolysis, dehydrogenation, oxidate transformation to ketone and carboxylate, N-dealkylation, and glucuronidation. Comparing our results with previous studies, the parent drugs and SC metabolites formed via hydrogenation, carboxylation, ketone formation, and oxidative defluorination were identified as suitable biomarkers.

Anti-proliferative activity of nitroquinolone fused acylhydrazones as non-small cell human lung cancer agents.

A new series of 8-nitroquinolone-based aromatic heterocyclic acyl hydrazones have been synthesised and characterised through various spectroscopic techniques. They were theoretically examined for molecular docking with various proteins related to the apoptosis of the non-small cell lung cancer cell line A549. The results indicate that the possible modes of interaction of all the synthesised compounds are compatible for use as anti-proliferative drugs. Also, the drug-likeness of the compounds was examined through theoretical ADMET analysis, which indicated good gastrointestinal absorption as well as low toxicity. Selected compounds were evaluated for their in vitro anti-cancer activity using A549, MCF-7 and HeLa cell lines through an MTT assay to determine cytotoxicity. Compounds 3c, 3a and 11c exhibited significant cytotoxicity towards A549 cells in the order of 3c (15.3 ± 0.7) > 3a (15.8 ± 0.1) > 11c (17.1 ± 0.2), whereas all the compounds show insignificant toxicity on normal human embryonic kidney cells up to a concentration of 200 μM. The best compounds among the series (3c and 11c) were chosen for further detection of apoptosis through fluorescence microscopic techniques using AO/EtBr and DAPI. The reduced DNA synthesis during the cell cycle was also investigated through flow cytometric techniques. The results indicate that the compounds possess significant anticancer properties due to the activation of the mitochondrial mediated intrinsic pathway.

Synthetic Transformation of 2-{2-Fluoro[1,1'-biphenyl]-4-yl} Propanoic Acid into Hydrazide-Hydrazone Derivatives: In Vitro Urease Inhibition and In Silico Study.

In the present study, 28 acyl hydrazones (4-31) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like 1H-NMR and HREI-MS and finally evaluated for in vitro urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC50 = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC50 = 21.14 ± 0.42 μM). Compound 30 was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, in silico molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme.

A linear tetranuclear Ni(II) acyl hydrazone Schiff base complex: preparation, crystal structure and catalytic application

A linear tetranuclear Ni(II) acyl hydrazone Schiff base complex: preparation, crystal structure and catalytic application