Aryl Hydrazones Research Articles

Synthesis of aryl hydrazone derivatives for α-naphthalide and benzothiazolide

تضمن البحث تحضير ثلاثة سلاسل من المركبات الجديدة من -N α –نفثايل -2-(اريل هيدرازونو)-3-اوكسو بيوتانمايد، و -N (6-كلورو بنزوثايزول -2-يل)-2-اريل هيدرازونو)-3-(اوكسو بيوتانمايد) ، -N (6-ميثل بنزوثايزول -2-يل)-2-اريل هيدرازونو)-3-(اوكسو بيوتانمايد) والمشتقة من النفثايل امين و2- امينوبنزوثايزول وقد أجريت التفاعلات بخطوتين :الخطوة الأولى كانت تفاعل النفثايل امين مع مثيل اسيتو اسيتيت للسلسلة الاولى وتفاعل مشتقات الامينو بنزوثايزول(6-كلوروامينو بنزوثايزول ،6-ميثل امينوبنزوثايزول ) مع مثيل اسيتو اسيتيت للسلسلة الثانية والثالثة على التوالي عند (160-170)م0 باستعمال طريقة حديثة في التحضير تزيد من النسبة المئوية للمنتوج. اما الخطوة الثانية فهي تفاعل هذه المركبات الناتجة مع املاح الاريل دايازونيوم كلورايد في وسط قاعدي وعند درجة (0-5) م0 للحصول على عشر صبغات جديدة من مشتقات الاريل هيدرازونو-3-اوكسو بيوتانمايد جميع هذه المركبات الجديدة تم تشخيصها بواسطة اطياف الاشعة تحت الحمراءFTIR وطيف الرنين النووي المغناطيسي13C-NMR, 1H-NMR وال UV-Visible وقياس درجات الانصهار وكذلك الذوبانية.

Synthesis, characterization and investigation of biological activities of Schiff base and its Ni(II) complex obtained from 2-Benzoylpyridine and 3-Hydroxy-2-naphthoic hydrazide

In this paper, a new aryl hydrazone and its Nickel (II) complex were synthesized from 2-benzoylpyridine and 3-Hydroxy-2-naphthoic hydrazide. The synthesized compounds were characterized by elemental analysis, UV Vis., IR, NMR spectral studies and mass spectra. The data indicate that the metal atom is coordinated by the two ligands and that the [NiL2] complex is octahedral. The ligand is coordinated through carbonyl-O, azomethine-N, and pyridyl-N atoms. When tested against various reference bacterial strains and clinical isolates, it was discovered that the antibacterial activity of the [NiL2] complex was more effective than the ligand.

Elemental Sulfur Promoted Cyclization of Aryl Hydrazones and Aryl Isothiocyanates Yielding 2-Imino-1,3,4-thiadiazoles.

We report a method for using elemental sulfur to facilitate the cyclization of aryl hydrazones and aryl isothiocyanates, affording biorelated 2-imino-1,3,4-thiadiazoles. Reactions progressed in the presence of elemental sulfur, N-methylmorpholine base, and DMSO solvent, while were tolerant of a wide range of functionalities including halogen, nitro, cyano, methylsulfonyl, and heterocyclic groups. The method appears to offer a general pathway for using simple, cheap, and stable reagents to afford triaryl-substituted 2-imino-1,3,4-thiadiazoles under relatively mild conditions.

Novel Radiochromic Elastomer Dosimeter Based on the Self-Sensitizing Effect of Disulfide Bonds.

γ-Irradiation is a kind of high-energy ionizing ray, which has widespread applications in material, food, and medical industries as well as in the environment. Since this irradiation is invisible, quantitatively monitoring its exposure doses is crucial to irradiated targets. As a type of dosimeter, radiochromic dosimeters can detect γ-irradiation by color changing, and its strategy to realize the radiochromic behavior basically relies on active radicals from radiolysis of an external environmental medium. However, the primary problem of this external environment-mediated sensitization strategy is that it complicates the components of dosimeters. Herein, we present a novel type of self-sensitizing radiochromic poly(urethane-urea) elastomers (PUUEs), where disulfide bonds, serving as radiation-responsive and sensitizing units, are introduced. This is the first attempt to utilize radicals generated from radiolysis of weak bonds in a solid polymer matrix to sensitize color change of dye-doped radiochromic dosimeters. Moreover, it is intriguing that the simultaneously introduced aryl hydrazone bond endows dosimeters with excellent color retention and maintains the Δa* value of 72.9% even after 1 month on the basis of the as-irradiated specimen. Besides, the metathesis of disulfide bonds not only endows dosimeters with better self-healing capability, but also accelerates the postcuring behavior and hydrogen bond reconfiguration, resulting in improved mechanical performance.

Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives

Two series of novel imidazo[1,2-a]pyridine-2-carbohydrazide derivatives have been designed, synthesized, and evaluated for cytotoxic activity. Target compounds were designed in two series: aryl hydrazone derivatives that were devoid of triazole moiety (7a-e) and aryl triazole bearing group (11a-e). In vitro cytotoxicity screening was carried out using MTT assay against three human cancer cells including breast cancer (MCF-7), colon cancer (HT-29), and leukemia (K562) cell lines as well as a non-cancer cell line (Vero). Compound 7d bearing 4-bromophenyl pendant from aryl hydrazone series exhibited the highest cytotoxic potential with IC50 values of 22.6 µM and 13.4 µM against MCF-7 and HT-29 cells, respectively, while it was not toxic towards non-cancer cells up to the concentration of 100 µM. Cell cycle analysis revealed that 7d increased the number of MCF-7 cells in the G0/G1 phase and also induced apoptosis in these cells as revealed by Hoechst 33,258 staining. The molecular mechanism contributing to the anti-proliferative effect of the most potent compound was investigated in silico using Super Pred software and introduced PDGFRA as a plausible target for 7d. Molecular docking and molecular dynamic studies demonstrated Lys627 and Asp836 as key residues interacting with the active compound. Overall, 7d could serve as a suitable candidate for further modifications as a lead anticancer structure.

Synthesis, Characterization, and Biological Activity of Di‐2‐pyridyl Ketone Aryl Hydrazone and Its Copper(II) Complex and the Interaction of Di‐2‐pyridyl Ketone Aryl Hydrazone with DNA Bases

AbstractThe development of antibiotic resistance has also increased the interest in hydrazones. In this paper, we describe the new aroyl hydrazone and its Cu(II) complex, which we synthesized. Aroyl hydrazone (HL) was prepared by the condensation reaction of 3‐hydroxy‐2‐naphthoic hydrazide with di‐2‐pyridyl ketone. Ligand (HL) and its transition metal complexes [CuL2] (1), have been characterized by elemental analysis, FT‐IR, UV‐Vis., 1H‐NMR, and LC–MS techniques. The molecular structure of HL, whose crystal structure could not be obtained, was elucidated by the DFT/B3LYP/6‐311+G(d, p) method. The optimized molecular structure, total energy, molecular orbital energy values, molecular electrostatic potential map, reactivity parameters, and interaction with DNA bases were investigated. Theoretical UV‐vis spectra of HL were obtained with TD‐DFT in different solvent environments. In addition, the ligand and its complex were examined for their antimicrobial activity against pathogenic microorganisms by using a minimal inhibitory concentration method (MIC). It was determined that the [CuL2] (1) complex was generally moderately active. It was also observed that the [CuL2] (1) complex was more active than the HL.

Organocatalytic Activation of Donor-Acceptor Cyclopropanes: A Tandem (3 + 3)-Cycloaddition/Aryl Migration toward the Synthesis of Enantioenriched Tetrahydropyridazines.

An organocatalytic enantioselective (3 + 3)-cycloaddition reaction of racemic cyclopropane carbaldehydes and aryl hydrazones has been demonstrated for the first time. A wide range of enantioenriched tetrahydropyridazines with an exocyclic double bond were obtained with moderate to good yields and good to excellent enantiomeric excesses. Mechanistic investigations hinted toward a matched/mismatched kinetic resolution, and control experiments and DFT calculations unveiled that 1,3-aryl migration was concerted and intramolecular and proceeds via a four-membered transition state.

Effects of an aryl hydrazone derivative of naproxen on HepG2 liver cancer and HGF gingival fibroblasts cell lines

Effects of an aryl hydrazone derivative of naproxen on HepG2 liver cancer and HGF gingival fibroblasts cell lines

Synthesis, anti-ferroptosis, anti-quorum sensing, antibacterial and DNA interaction studies of chromene-hydrazone derivatives

Nineteen chromene-hydrazone derivatives containing a variety of structural modifications on the hydrazone moiety were synthesized. Structure-activity correlations were investigated to determine the influence of structural variations on anti-ferroptosis, anti-quorum sensing, antibacterial, DNA cleavage and DNA binding properties. Ferroptosis inhibitory activity was determined by measuring the ability of the derivatives to reverse erastin-induced ferroptosis. Several of the derivatives were more effective than fisetin at inhibiting ferroptosis, with the thiosemicarbazone derivative being the most effective. Quorum sensing inhibition was evaluated using Vibrio harveyi, and both V. harveyi and Staphylococcus aureus were used to determine antibacterial activity. The semicarbazone and benzensulfonyl hydrazone derivatives showed moderate quorum sensing inhibition with IC50 values of 27 μM and 22 μM, respectively, while a few aryl hydrazone and pyridyl hydrazone derivatives showed bacterial growth inhibition, with MIC values ranging from 3.9 to 125 μM. In addition, the interaction of the hydrazone derivatives with DNA was investigated by gel electrophoresis, UV–Vis spectroscopy and molecular docking. All of the derivatives cleaved plasmid DNA and showed favorable interaction with B-DNA through minor groove binding. Overall, this work highlights a broad range of pharmacological applications for chromene-hydrazone derivatives.

Defluoroalkylation of Trifluoromethylarenes with Hydrazones: Rapid Access to Benzylic Difluoroarylethylamines.

Here, we report an efficient and modular approach toward the formation of difluorinated arylethylamines from simple aldehyde-derived N,N-dialkylhydrazones and trifluoromethylarenes (CF3-arenes). This method relies on selective C-F bond cleavage via reduction of the CF3-arene. We show that a diverse set of CF3-arenes and CF3-heteroarenes react smoothly with a range of aryl and alkyl hydrazones. The β-difluorobenzylic hydrazine product can be selectively cleaved to form the corresponding benzylic difluoroarylethylamines.

Reversible Colorimetric and Fluorescence Solid Sensors Based on Aryl Hydrazone Derivatives of 1,8-Naphthalimides for Caustic Media and Biogenic Amine Vapors

Fluorescence and colorimetric solid sensors for caustic media and biogenic amine vapors have been prepared. For this purpose, several hydrazone derivatives of naphthalimides were synthesized and anchored to a photo-crosslinked membrane functionalized with acid chloride groups. The membranes were characterized using different techniques, and their thermal properties and swelling degree were determined. The new naphthalimides and the membranes were evaluated as sensors by determining the change in their spectroscopic properties of absorption and fluorescence with pH. The polymeric sensors exhibit improved stability and can be reused, as a consequence of their solid character and the reversibility of the process. Furthermore, membranes were evaluated as a sensor of trimethylamine vapors through their absorption and fluorescence bands, and the color change in the membrane showed that it could be used to detect basic media with the naked eye. Finally, membranes were packaged in Petri dishes at a controlled temperature with fresh fish bought in the local market. Then, the real chance of using the sensory materials was determined by analyzing the color change in samples.

Multi-component reactions of cyclohexan-1,3-dione to synthesize heterocyclic derivatives with c-Met enzymatic activity, anti-prostate, anti-proliferative and tyrosine kinase activities

ABSTRACT. We are aiming in this work to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from aryl hydrazones of cyclohexan-1,3-dione followed by its heterocyclization reactions to produce anticancer molecules. The multi-component reactions of the arylhydrazocyclohexan-1,3-dione derivatives 3a-c produced the 1,4,5,6,7,8-hexahydroquinoline derivatives 6a-r and the 4,5,6,8-tetrahydrochromeno[2,3-c]pyrazole derivatives 10a-c. Other multi-component reactions were demonstrated. The anti-proliferative activity of the synthesized compounds toward the six cancer cell lines namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition the c-Met enzymatic activities and inhibition toward the prostate cancer cell PC-3 were measured. The results obtained in most cases, indicated that the presence of electronegative Cl group through the molecule favour the inhibitions.
 
 KEY WORDS: Multi-component reactions, Cyclohexan-1,3-dione, Chromene, Chromeno[2,3-c]pyrazole, Cytotoxicity
 
 Bull. Chem. Soc. Ethiop. 2022, 36(1), 119-136. 
 DOI: https://dx.doi.org/10.4314/bcse.v36i1.11 

Direct gem-Difluoroalkenylation of X-H Bonds with Trifluoromethyl Ketone N-Triftosylhydrazones for Synthesis of Tetrasubstituted Heteroatomic gem-Difluoroalkenes.

The direct gem-difluoroalkenylation of X-H bonds represents the most straightforward approach to access heteroatomic gem-difluoroalkenes that, as the isostere of the carbonyl group, have great potency in drug discovery. However, the construction of tetrasubstituted heteroatomic gem-difluoroalkenes by this strategy is still an unsolved problem. Here, we report the first direct X-H bond gem-difluoroalkenylation of amines and alcohols with trifluoromethyl ketone N-triftosylhydrazones under silver (for (hetero)aryl hydrazones) or rhodium (for alkyl hydrazones), thereby providing a most powerful method for the synthesis of tetrasubstituted heteroatomic gem-difluoroalkenes. This method features a broad substrate scope, high product yield, excellent functional group tolerance, and operational simplicity (open air conditions). Moreover, the site-specific replacement of the carbonyl group with a gem-difluorovinyl ether bioisostere in drug Trimebutine and the post-modification of bioactive molecules demonstrates potential use in medicinal research. Finally, the reaction mechanism was investigated by combining experiments and DFT calculations, and disclosed that the key step of HF elimination occurred via five-membered ring transition state, and the difference in the electrophilicity of Ag- and Rh-carbenes as well as the multiple intermolecular interactions rendered the effectiveness of Rh catalyst selectively for alkyl hydrazones.

Synthesis, Computational and cytotoxicity studies of aryl hydrazones of β-diketones: Selective Ni2+ metal Responsive fluorescent chemosensors

A new fluorescent sensor 2-(2-(3-chloro-4-fluorophenyl)hydrazono)-5,5-dimethyl cyclohexane-1,3-dione (A) and 2-(2-(4-chloro-2-nitrophenyl)hydrazono)-5,5-dimethyl cyclohexane-1,3-dione (B) composed of a β-diketones of aryl hydrazones synthesized by simple and cost-effective method. Various analytical tools analyzed the structural investigations of the synthesized substituted β-diketones of aryl hydrazones like FT-IR, 1H, 13C NMR and UV–Vis techniques, Single-crystal X-ray diffraction studies (SCXRD) (for A), Scanning electron microscopy (SEM), and fluorescence spectroscopy. SEM also investigates surface morphology modifications of aryl hydrazones and Ni2+ complex. Furthermore, the metal sensing (Chemo sensing) behavior of newly prepared aryl hydrazones of β-diketones derivatives was further studied by fluorescence spectroscopy. The aryl hydrazones sensor materials show admirable fluorescence selectivity with enrichment to Ni2+ over different cations in an aqueous ethanol solution with a recognition extremity of 4 μM–7 μM. A joint experimental and theoretical investigation was led on the chemical structure employing a density functional theory (DFT) (B3LYP), engaging a 6-31G basis set. The DFT technique's enhanced geometrical bond angles and lengths exhibited great covenant with the experimental results. The highest occupied molecular (HOMO) orbital and lowest unoccupied (LUMO) molecular orbital energy has been concluded. The cytotoxicity studies show these compounds impede the growth of KB cells highly and from the studies to evaluate their capability to accurately dock aryl hydrazones to antibodies of cancer protein such as 4LRH, 4L9K, 4 EKD and 4GIW cancer proteins.

Synthesis, structural elucidation, DFT calculation, biological studies and DNA interaction of some aryl hydrazone Cr3+, Fe3+, and Cu2+ chelates

The current research focuses on the treatment of Cr(III), Fe(III) and Cu(II) metal ions with aryl hydrazone ligand named (E)-4-(((diphenylmethylene)hydrazono)methyl)benzene-1,3-diol (DPHB) to afford four novel solid complexes with high yields. Different characterization approaches, including infrared, UV–visible, and NMR spectroscopies, elemental analyses, and thermal gravimetric analysis (TGA), revealed that all mononuclear crystalline metal chelates with good thermal stability had a six-coordination with octahedral geometry. Density Functional Theory (DFT) computations were used and provided a reasonable explanation for these metal chelates' electrical and structural features. Furthermore, investigations of electronic absorption spectroscopy, hydrodynamics, and electrophoresis demonstrated that these new compounds interact with calf thymus deoxyribonucleic acid (CT-DNA) in a variety of ways. As a result, the Kb and ∆Gb≠ values of such interactions were in the following order: DPHBCu > DPHBCr > DPHBFe complex. Additionally, the novel metal chelates have been studied anti-bathogenically and found to be significantly effective compared to the comparable DPHB hydrazone ligand. The anti-proliferative activities of the investigated compounds were also evaluated against different lines of cancer cells and exhibited significant cytotoxic activity. In addition, observations of antioxidant activity suggest that antioxidant activity relative to ordinary ascorbic acid was demonstrated in the molecule.

Pharmacophore Based Design, Synthesis and Theoretical Conformational Analysis of Some Extended Aryl Hydrazones as Potential Anticonvulsant

A series of hydrazones were synthesized by condensing substituted hydrazides with appropriate carbonyl compounds. The chemical structures of the synthesized compounds were confirmed by infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, mass ((4-chloro-phenylamino)-acetic acid [1-(4-chlorophenyl)-phenyl-methylene]-hydrazide and (2,4-dichloro-phenylamino)-acetic acid (3-oxo- 1,3-dihydro-indole-2-ylidene)-hydrazide only) spectral data and carbon hydrogen nitrogen analysis. The title compounds were screened for their anticonvulsant activity against mice at doses of 30 mg/kg, 100 mg/kg and 300 mg/kg. The preliminary anticonvulsant screening data of this series resulted in the identification of two lead compounds (2,4-dichloro-phenylamino)-acetic acid (3-oxo-1,3-dihydro-indole- 2-ylidene)-hydrazide and (2,4-dichloro-phenylamino)-acetic acid [1-(4-chlorophenyl)-phenyl-methylene]- hydrazide with excellent preliminary anticonvulsant profile with no neurotoxicity in maximal electroshock seizure and subcutaneous metrazol mice model.

Spectroanalytical, computational, DNA/BSA binding and in vitro cytotoxic activity studies of new transition metal complexes of novel aryl hydrazone

The ligand ((1-ethyl-Nʹ-furan-2-yl)-methylene)-1,4-dihydro-7-methyl-4-oxo-1,8- napthyridine-3-carbohydrazide (NFMHMONC) and its transition metal (II) complexes were synthesized and characterized by various spectroanalytical techniques. The quantum chemical calculations and physicochemical properties of NFMHMONC were evaluated by HyperChem 7.5 software tools. The binding ability of metal complexes with CT-DNA has been determined by electronic absorption spectral titrations and competitive DNA binding fluorescence measurements showed a relatively high binding constant value in [Cu(II)(NFMHMONC)2]Cl2 compared to [Co(II)(NFMHMONC)2H2O]Cl2. The DNA binding behaviors were investigated by the study of viscosity measurement and the results indicated the intercalative mode of binding. The binding efficiency of metal complexes with BSA was also determined by electron absorption spectroscopy. Hydrolytic cleavage activity against supercoiled pBR322 plasmid DNA of NFMHMONC and its metal (II) complexes carried out and inferred more efficient double-strand DNA cleavage with [Cu(II)(NFMHMONC)2]Cl2 complex. The radical scavenging activity study of NFMHMONC and its metal complexes evaluated by their interaction with the DPPH free radical on electronic absorption spectroscopy has shown remarkable antioxidant activity. In vitro cytotoxicity studies revealed a lower percentage of cell viability and IC50 value in both HeLa and MCF-7 cell lines with [Cu(II)(NFMHMONC)2]Cl2 compared to [Co(II)(NFMHMONC)2H2O]Cl2 and NFMHMONC.

Aryl hydrazones linked thiazolyl coumarin hybrids as potential urease inhibitors

Aryl hydrazones linked thiazolyl coumarin hybrids as potential urease inhibitors

Tailoring, structural elucidation, DFT calculation, DNA interaction and pharmaceutical applications of some aryl hydrazone Mn(II), Cu(II) and Fe(III) complexes

The current research focuses on the treatment of Mn(II) Cu(II) and Fe(III) metal ions with 1-(Benzhydrylidene-hydrazonomethyl)-naphthalen-2-ol (aryl hydrazone DHPN) ligand, producing three new solid complexes with substantial yields. In all mononuclear crystalline metal chelates with high thermal stability, different characterization techniques including infrared, UV–visible and NMR spectroscopies, elemental analyses and TGA revealed a tetra-coordination in DPHNCu complex and six-coordination for DPHNMn and DPHNFe complexes. Calculations based on Density Functional Theory (DFT) were used and offered a satisfactory explanation to better understands the electronic and structural properties of these metal chelates. Moreover, electronic absorption spectroscopy, hydrodynamic and electrophoresis measurements have revealed significant interactions of these novel complexes with calf thymus DNA through different binding modes. Accordingly, the Kb and ΔGb≠ values of such interaction followed that order: DPHNFe > DPHNMn > DPHNCu complex. In addition to, antibathogenic studies of the new metal chelates revealed that the latter had considerably high efficacy than the corresponding hydrazone ligand. The anti-proliferative activity of the compounds studied was also tested against various cancer cell lines and showed substantial cytotoxic activity. Moreover, antioxidant activity findings showed that the compounds tested had anti-oxidative activity relative to regular ascorbic acid. Furthermore, docking study of the investigated DPHN ligand and its complexes was performed to get a first insight of the interaction in the active site of the protein enzyme of the bacteria and fungi receptors.

Cobalt-Catalyzed C-H Activation and [3 + 2] Annulation with Allenes: Diastereoselective Synthesis of Indane Derivatives.

An unprecedented bidentate directing-group-assisted cobalt-catalyzed oxidative C-H activation of aryl hydrazones followed by a syn-diastereoselective [3 + 2] annulation reaction has been achieved, employing allenes as the annulation partners. The selective 2,3-migratory insertion of allenes with arylcobalt(III) species and the subsequent intramolecular diastereoselective nucleophilic addition of η1-allylcobalt onto the imine resulted in [3 + 2] annulation over the alternative [4 + 2] annulation. Furthermore, the oxidative annulation obviates the need for stoichiometric metal oxidants and proceeds under aerobic conditions.