Hydrazone Derivatives Research Articles

In-silico molecular docking, ADMET and DFT evaluation of piperidin-4-one furoic hydrazone derivatives as antimicrobial, antioxidant and anticancer agents

In-silico molecular docking, ADMET and DFT evaluation of piperidin-4-one furoic hydrazone derivatives as antimicrobial, antioxidant and anticancer agents

Highly sensitive fluorescent hydrazone derivatives for sensing of Cu2+ and its application for actual environment detection

Two novel fluorescent probes PF and KF based on hydrazine, coumarin/quinoline and pyrimidine motif were synthesized. Both of them showed great turn-off fluorescence response to Cu2+ in aqueous solution, which was accompanied by a significant change from bright green and blue fluorescence to dark. They possessed satisfactory detection performances to Cu2+ including specific selectivity and anti-interference, low detection limit, fast response and recyclability. In addition, they were successfully used for paper-based indicators that can be easily applied for naked-eye detection of Cu2+ as expected. Probe PF was also successfully used for portable detection of Cu2+ by smartphone sensing platform and in real water samples. DFT calculations and systematic experiment research indicated possible mechanism was that Cu2+ bound to fluorophore molecules through spin–orbit coupling effect, formation of PF/KF + Cu2+ complex led to fluorescence quenching.

HTIB as an Efficient and Convenient Reagent for Oxidative Cleavage of C=N in Pyrimidinyl Hydrazones

This study is aimed to explore the efficiency of [hydroxy(tosyloxy)iodo]benzene (HTIB) in the oxidative cleavage of some pyrimidinyl hydrazones. The protocol involves stirring the hydrazone derivatives with HTIB in dichloromethane at room temperature. The oxidative cleavage of C = N in pyrimidinyl hydrazones regenerated parent ketones in high yields. The methodology has advantage of preventing over oxidation of carbonyl functionality.. KEYWORDS :[Hydroxy(tosyloxy)iodo]benzene, Hydrazone, Hypervalent iodine reagent, Oxidative cleavage, Pyrimidine.

Synthesis of 3-hydroxy-2-naphthohydrazide-based hydrazones and their implications in diabetic management via in vitro and in silico approaches.

Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, "α-glucosidase." Several approaches including fourier transform infrared, 1 H NMR, and 13 C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a-3p displayed more effective inhibitory activities against α-glucosidase with IC50 in a range of 2.80-29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration-dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, anin silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene-ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α-glucosidase enzyme.

Design, synthesis and anticancer evaluation of novel arylhydrazones of active methylene compounds

Nerve growth factor (NGF) and its receptor, tropomyosin kinase receptor kinase type A (TrkA) is emerging as an important target for Glioblastoma (GBM) treatment. TrkA is the cancer biomarker majorly involved in tumor invasion and migration into nearby normal tissue. However, currently, available Trk inhibitors exhibit many adverse effects in cancer patients, thus demanding a novel class of ligands to regulate Trk signaling. Here, we exploited the role of TrkA (NTRK1) expression from the 651 datasets of brain tumors. RNA sequence analysis identified overexpression of NTRK1 in GBM, recurrent GBM as well in Oligoastrocytoma patients. Also, TrkA expression tends to increase over the higher grades of GBM. TrkA protein targeting hydrazone derivatives, R48, R142, and R234, were designed and their mode of interaction was studied using molecular docking and dynamic simulation studies. Ligands' stability and binding assessment reveals R48, 2 2-(2-(2-hydroxy-4-nitrophenyl) hydrazineylidene)-1-phenylbutane-1,3-dione, as a potent ligand that interacts well with TrkA's hydrophobic residues, Ile, Phe, Leu, Ala, and Val. R48- TrkA exhibits stable binding potentials with an average RMSD value <0.8 nm. R48 obeyed Lipinski's rule of five and possessed the best oral bioavailability, suggesting R48 as a potential compound with drug-likeness properties. In-vitro analysis also revealed that R48 exhibited a higher cytotoxicity effect for U87 GBM cells than TMZ with the IC50 value of 68.99 μM. It showed the lowest percentage of cytotoxicity to the non-cancerous TrkA expressing MEF cells. However, further SiRNA analysis validates the non-specific binding of R48, necessitating structural alteration for the development of R48-based TrkA inhibitor for GBM therapeutics.

Synthesis, characterization, DNA binding, DFT, anticancer, antibacterial, and the effect of gamma irradiation of novel Co(II), Ag (I), and Cd (II) complexes with hydrazone derivatives

Three new Co (II), Ag (I), and Cd (II) ion complexes were created from the ligand, 2-(phenylglycyl)-N-(p-tolyl)hydrazine-1-carbothioamide (H2LB). The structural makeup of the new compounds was clarified using analytical and spectroscopic techniques. Then, using the Gaussian09 software, geometry optimization was done for each synthesis. Furthermore, the compound's antibacterial and anticancer properties were evaluated against different types of bacteria and the HepG2 cell line using non-irradiated and irradiated complexes, where the complex (A1) is higher than them. It was proposed that only an intercalation or replacement technique was used when the ligand and complexes [Co(H2L)(NO3)2]H2O (B1, A1) interacted with CT-DNA. Calculations were made for the intrinsic binding constant Kb. According to a molecular docking study, the ligands and complexes revealed fascinating interactions with the amino acids in the ribosyltransferase active site. (Code: 3GEY).

Synthesis, Crystal Structure, Hirshfeld Surface Analysis and Computational Study of Hydrazone Derivative of 5,5-dimethylcyclohexane-1,3-dione

Synthesis, Crystal Structure, Hirshfeld Surface Analysis and Computational Study of Hydrazone Derivative of 5,5-dimethylcyclohexane-1,3-dione

Synthesis and ultraviolet/aggregation-induced emission investigation of novel tetraphenylvinyl hydrazone derivatives: efficient multimodal chemosensors for fluoride ion

Synthesis and ultraviolet/aggregation-induced emission investigation of novel tetraphenylvinyl hydrazone derivatives: efficient multimodal chemosensors for fluoride ion

Synthesis, Biological Evaluation and Theoretical Studies of Hydrazone Derivatives

The aim of this work is to synthesize, characterize and evaluate the biological activity of a series of hydrazone derivatives. These compounds were characterized by elemental analysis, IR spectroscopy, mass spectrometry, UV-Vis Spectroscopy, 1HNMR spectra. In vitro, their antibacterial and antifungal activities were screened against bacterial species (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) and fungi (Candida sp). Amikacin was used as references for antibacterial and antifungal studies. The compounds were optimized at DFT/B3LYP/6-31G (d,p) level of theory. In silico, The Toxicity of the hydrazone derivatives were studied by ADMET(Absorption, distribution, metabolism, excretion, and toxicity) simulations using ADMET lab 2.0 server. The molecular docking studies are carried out to better comprehend the preferential mode of binding of these compounds against biomecular targets such as InhA enzyme characteristic of Mycobacterium Tuberculosis bacteria.

Anticancer and Antiphytopathogenic Activity of Fluorinated Isatins and Their Water-Soluble Hydrazone Derivatives.

A series of new fluorinated 1-benzylisatins was synthesized in high yields via a simple one-pot procedure in order to explore the possible effect of ortho-fluoro (3a), chloro (3b), or bis-fluoro (3d) substitution on the biological activity of this pharmacophore. Furthermore, the new isatins could be converted into water-soluble isatin-3-hydrazones using their acid-catalyzed reaction with Girard's reagent P and its dimethyl analog. The cytotoxic action of these substances is associated with the induction of apoptosis caused by mitochondrial membrane dissipation and stimulated reactive oxygen species production in tumor cells. In addition, compounds 3a and 3b exhibit platelet antiaggregation activity at the level of acetylsalicylic acid, and the whole series of fluorine-containing isatins does not adversely affect the hemostasis system as a whole. Among the new water-soluble pyridinium isatin-3-acylhydrazones, compounds 7c and 5c,e exhibit the highest antagonistic effect against phytopathogens of bacterial and fungal origin and can be considered useful leads for combating plant diseases.

Design, Synthesis, and Antifungal Activity of Novel 2-Ar-1,2,3-Triazole Derivatives.

Triazoles are crucial molecular frameworks in the development of fungicidal compounds. Although there has been extensive research on triazole derivatives for fungicide discovery, the investigation of 2-Ar-substituted-1,2,3-triazoles remains in progress. This study reports the synthesis and evaluation of the fungicidal activity of 27 distinct 2-Ar-substituted-1,2,3-triazole derivatives. These derivatives were synthesized from anilines through a three-step process, with the key step being the Cu(II)-catalyzed annulation reaction of readily accessible alkyl 3-aminoacrylates with aryldiazonium salts. All derivatives were novel, and their structures were characterized using 1H NMR, 13C NMR, and high-resolution mass spectrometry. Their antifungal activity was tested against five phytopathogenic fungi. Twelve of the target compounds exhibited better performance than the positive control hymexazol in the fungal test. Notably, compound 6d demonstrated the most potent inhibition against Botryosphaeria dothidea with an EC50 value of 0.90 mg/L. The structure-activity relationships are also discussed in this paper. Preliminary studies on the antifungal mechanism of compound 6d revealed that it inhibits ergosterol synthesis and alters the morphology and ultrastructure of the B. dothidea mycelium. These results suggest that the designed 2-Ar-substituted-1,2,3-triazole-containing hydrazone derivatives warrant further investigation as potential lead compounds for novel antifungal agents.

Escherichia coli Nissle 1917-driven microrobots for effective tumor targeted drug delivery and tumor regression.

Potent tumor regression remains challenging due to the lack of effective targeted drug delivery into deep tumors as well as the reduced susceptibility of cancer cells to anticancer agents in hypoxic environments. Bacteria-driven drug-delivery systems are promising carriers in overcoming targeting and diffusion limits that are inaccessible for conventional antitumor drugs. In this study, probiotic facultative anaerobe Escherichia coli Nissle 1917 (EcN) was functionalized and formed self-propelled microrobots to actively deliver therapeutic drug and photosensitizer to the deep hypoxic regions of tumors. Doxorubicin (Dox) was firstly modified with cis-aconityl anhydride (CA) and terminal thiol-decorated hydrazone derivative (Hyd-SH) through dual pH-sensitive amide and imine bonds, respectively. The functionalized CA-Dox-Hyd-SH was further coordinated with photosensitizer gold nanorods (AuNRs) and then conjugated to the surface of EcN. The resulting microrobots (EcN-Dox-Au) inherited the mobility characteristics and bioactivity of native EcN. Upon the irradiation of NIR laser, the microrobots exhibited enhanced tumor accumulation and penetration into the deep hypoxia tumor site. Strikingly, after 21 days of treatment with EcN-Dox-Au formulations, complete tumor regression was achieved without relapse for at least 53 days. This self-propelled strategy utilizing bacteria-driven microrobots provides a promising paradigm for enhancing drug penetration and elevating chemosensitivity, resulting in a superior antitumor effect. STATEMENT OF SIGNIFICANCE: Self-propelled Escherichia coli Nissle 1917 (EcN) - mediated microrobots are functionalized to co-deliver therapeutic drugs and photosensitizers to the deep tumor site. Anti-tumor drug doxorubicin (Dox) was modified through dual pH-sensitive bonds on both terminals and then linked with EcN and photosensitizer gold nanorods (AuNRs) to realize tumor microenvironment acidic pH-responsive drug release. Upon irradiation with a NIR laser near the tumor site, AuNRs produced a photothermal effect which realized the superficial tumor thermal ablation and increased the permeability of the tumor cell membrane to facilitate the penetration of microrobots. Moreover, the deep penetration of microrobots also enhanced the susceptibility of the cancer cells to Dox, and realized the complete tumor regression in the established breast cancer-bearing mice without recurrence using a lower dose of drug regimen.

Water Bath Sonicator As An Eco-friendly Technique for Synthesis of New Dihydrazide Hydrazone Derivatives

Water Bath Sonicator As An Eco-friendly Technique for Synthesis of New Dihydrazide Hydrazone Derivatives

Rhodamine hydrazide-linked naphthalimide derivative: Selective naked eye detection of Cu2+, S2− and understanding the therapeutic potential of the copper complex as an anti-cervical cancer agent

A naphthalimide-labeled rhodamine hydrazone derivative HL has been synthesized, characterized and examined in metal ion recognition. It shows selective colorimetric detection of Cu2+ over a number of other metal ions with a detection limit of 1.66 × 10−7 M in CH3CN/HEPES buffer (v/v = 2:1, pH = 6.8). The spirolactam ring of rhodamine and the imino-phenol motif of naphthalimide in HL are involved in complexation of Cu2+ as shown by single crystal X-ray. Single crystal of the copper-complex is prepared by utilizing NaSCN and it is characterized as CuL(SCN). The emergence of new absorption at 550 nm in UV–vis and the pink color of the solution reveal the selective interaction toward Cu2+. HL is characterized as a fluorescence resonance energy transfer (FRET) system that remains ‘turned OFF’ while spirolactam ring exists. In the presence of Cu2+, FRET is ‘turned ON’ via the opening of spirolactam ring to give emission at 580 nm which is less intense due to the quenching effect of Cu2+ ion. The complexation is reversible and the ensemble of Cu2+.HL selectively recognizes S2− over a series of different anions involving a color change from pink to colorless via the formation of spirolactam ring. The copper complex CuL(SCN) is further employed to understand its efficacy as a therapeutic agent. The complex is cytotoxic to high-risk HPV positive cervical cancer cell lines like SiHa and HeLa and is efficient in the generation and accumulation of reactive oxygen species (ROS). The complex also initiates nuclear blebbing and shows DNA degradation as understood by DNA laddering assay.

A Review on Synthesis, Lanthanide Complexes and Biological Activites of Hydrazone Derivatives of Hydrazinecarbothioamides

Hydrazinecarbothioamides are important intermediates with biological activities in organic chemistry synthesis, especially in the synthesis of biologically active heterocyclic scaffolds and compounds. The uniqueness in of synthesis and a wild range of pharmaceutical, medicinal biological potentials and properties, their preferred application as building brick in and the synthesis of heterocyclic and other important organic compounds and nonlinear optical (NLO) materials have made them attractive derivatives of thiosemicarbazides in the recent years. In this review, a detailed account in terms of synthesis and applications of their hydrazone derivatives and their lanthanide complexes are presented .Further, the biological and analytical applications of newly reported ligands and their complexes are reported. The wide investigation of the lanthanide (III) coordination complexes with organic ligands are mainly due to their structures and strong potential biological and pharmacological properties of hydrazones as derivatives of hydrazinecarbothioamides possess sites that play important roles in the formation of heterocyclics and other biologically active scaffolds.

Synthesis of New Hydrazone Derivatives of Nipagin and Determination of their in Silico Biological Activities

Bu çalışmada nipagin’den (metil paraben, metil-4-hidroksibenzoat) hareketle yeni seçici ve düşük toksisiteye sahip potansiyel anti kanser ajanlar geliştirilmesi amacıyla arilidenhidrazid yapısında sekiz adet bileşik (4-11) sentezlendi ve bu bileşiklerin meme kanseri büyüme faktörü reseptörü olan HER2’ye karşı etkinlikleri in siliko yöntemlerle ilk defa araştırıldı. Öncelikle moleküler docking çalışmaları ile hedef bileşiklerin ilgili protein üzerindeki bağlanma skorları ve serbest bağlanma enerjileri belirlendi, daha sonra moleküler dinamik çalışmaları ile protein-ligand komplekslerinin kararlılıkları incelendi ve son olarak bileşiklerin tahmini ADME parametreleri hesaplandı. Sentezlenen bütün bileşikler 1H NMR, 13C NMR, FT-IR ve HRMS analizleri ile karakterize edildi. Moleküler doking çalışmalarının sonuçlarına göre en aktif molekülün, -10.098 kcal/mol docking skoru ve -64.97 kcal/mol serbest bağlanma enerjisine sahip bileşik Bold olduğu belirlendi. Bileşik 6-HER2 ligand-protein kompleksinin moleküler dinamik simülasyonunda simülasyon zamanının %70’i boyunca hidrojen bağı ve pi-pi staking etkileşimlerinin devam ettiği ve ligand atomlarının RMSD değerlerinin ortalamasının 2Å olduğu tespit edildi. Hedef bileşiklerin in siliko ADME parametrelerinin referans aralıklarda olduğu ve tahmini ADME sonuçlarına göre ilaç benzerliği taşıdığı görüldü. Ayrıca sonuçlar referans antikanser ilaç doksorubisinin ile karşılaştırıldı ve bazı parametrelerin doksorubisine göre daha anlamlı ve uygun olduğu tespit edildi. Sonuç olarak ilk defa bu çalışmada sentezlen bileşik Bold, meme kanserinin büyüme faktörü reseptörü olan HER2’ye karşı yapılan in siliko çalışmalara göre en iyi inhibitör adayı olabileceği belirlendi.

ANTIOXIDANT ACTIVITY OF QUINOXALYL HYDRAZONES OF 2-HYDROXYIMINO-1,3-DICARBONYL COMPOUNDS

Biosimilarity and pharmacokinetic descriptors were obtained using SwissADME and ADMETlab 2.0 web services. Analysis of the obtained descriptors shows that, according to Lipinski’s rule, quinoxalyl hydrazones of 2-hydroximino-1,3-dioxocompounds may be promising candidates for drug development for oral administration. Analysis of the pharmacokinetic descriptors of the structures studied shows that, according to the in silico predictions, the compounds can penetrate the blood-brain barrier, be absorbed in the gastrointestinal tract, bind to plasma proteins, be rapidly eliminated from target cells and inhibit CYP3A4, CYP1A2, CYP2C19 and CYP2D6 isoenzymes. The antioxidant activity of quinoxalyl hydrazone derivatives with different benzoyl, ester and acetyl moieties has been studied. Pharmacological screening of the obtained compounds was performed in vitro in the model of Fe2+-induced lipid peroxidation. The data of pharmacological screening indicate clearly pronounced inhibition of lipid peroxidation in the system of yolk lipoproteins by the compounds obtained, which indicates a significant contribution of quinoxalone scaffold in the manifestation of antioxidant properties. Variations in the structure of the starting 1,3-dicarbonyl compounds did not result in significant changes in the antioxidant activity of the obtained hydrazones. The compounds obtained can be promising compounds with marked antioxidant activity for further in vivo studies, including investigation of acute and chronic toxicity. The leading compound is tolyl-substituted quinoxalyl hydrazone IIb

Synthesis of 4-(1-(2-(2,4-dinitrophenyl)hydrazineylidene)-5-phenylpenta-2,4-dien-1-yl)-1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazole as optical sensor for the toxic heavy metal ions in an aqueous medium

Heavy metal ions represented as highly toxic pollutants for the environment. In the search for new optical sensors for heavy metals, here, new organic linker [4-(1-(2-(2,4-dinitrophenyl)hydrazineylidene)-5-phenylpenta-2,4‑dien-1-yl)-1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazole] was prepared in 87% yield by simple and facile method. The techniques of synthesis follow the formation of chalcone then condensation with hydrazine moiety to perform hydrazone derivatives. It was synthesized from addition of 1-(1-(4-Methoxyphenyl)-5-methyl-1H-1,2,3-triazol-4-yl)-5-phenylpenta-2,4‑dien-1-one to 2,4-dinitrophenylhdrazine. The chemical structure of prepared linker was established by the IR and NMR spectral data in addition to single-crystal X-ray crystallography. The new linker was used for detection of various metal ions (Cu2+, Zn2+, Cr3+, Co2+, Cd2+, and Hg2+). Interestingly, the new linker showed highly detection level and selectivity toward Hg2+ions. The color of the Hg2+ ions solution was turned from colorless to green when adding the title compound performed excellent naked-eye detection. The binding stoichiometry of the linker to the Hg2+ ions was found to be 1:1, which was confirmed by Job plot. For industrial application, the new linker was mixed with filter paper and used for detection of Hg2+ions. The new fabricated filter paper was identified using scanning electron microscopy (SEM). The present fabricated filter paper produced naked eye colorimetric detection of Hg2+ions.

Quinoline Hydrazone Derivatives as New Antibacterials Against Multidrug Resistant Strains.

To develop novel antimicrobial agents a series of 2(4)-hydrazone derivatives of quinoline were designed, synthesized and tested. QSAR models of the antibacterial activity of quinoline derivatives were developed by the OCHEM web platform using different machine learning methods. A virtual set of quinoline derivatives was verified with a previously published classification model of anti-E. coli activity and screened using the regression model of anti-S. aureus activity. Selected and synthesized 2(4)-hydrazone derivatives of quinoline exhibited antibacterial activity against the standard and antibiotic-resistant S. aureus and E. coli strains in the range from 15 to 30 mm by the diameter of growth inhibition zones. Molecular docking showed the complex formation of the studied compounds into the catalytic domain of dihydrofolate reductase with an estimated binding affinity from -8.4 to -9.4 kcal/mol.

Unraveling the anti-corrosion mechanisms of a novel hydrazone derivative on steel in contaminated concrete pore solutions: An integrated study

IntroductionCorrosion-induced deterioration of infrastructure is a growing global concern. The development and application of corrosion inhibitors are one of the most effective approaches to protect steel rebar from corrosion. Hence, this study focuses on a novel hydrazone derivative, (E)-N′-(4-(dimethylamino)benzylidene)-2-(5-methoxy-2-methyl-1H-indol-3-yl)aceto-hydrazide (HIND), and its potential application to mitigate corrosion in steel rebar exposed to chloride-contaminated concrete pore solutions (ClSCPS). ObjectivesThe research aims to evaluate the anti-corrosion capabilities of HIND on steel rebar within a simulated corrosive environment, focusing on the mechanisms of its inhibitory effect. MethodsThe corrosion of steel rebar exposed to the ClSCPS was studied through weight loss and electrochemical methods. The surface morphology of steel rebar surface was characterized by FE-SEM-EDS, AFM; oxidation states of the steel rebar and crystal structures were examined using X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) methods. Further, experimental findings were complemented by theoretical studies using self-consistent-charge density-functional tight-binding (SCC-DFTB) simulations. The performance of HIND was monitored at an optimal concentration over a period of 30 days. ResultsThe results indicated a significant reduction in steel rebar corrosion upon introducing HIND. The inhibitor molecules adhered to the steel surface, preventing further deterioration and achieving an inhibition efficiency of 88.4% at 0.5 mmol/L concentration. The surface morphology analysis confirmed the positive effect of HIND on the rebar surface, showing a decrease in the surface roughness of the steel rebar from 183.5 in uninhibited to 50 nm in inhibited solutions. Furthermore, SCC-DFTB simulations revealed the presence of coordination between iron atoms and HIND active sites. ConclusionThe findings demonstrate the potential of HIND as an effective anti-corrosion agent in chloride-contaminated environments. Its primary adsorption mechanism involves charge transfer from the inhibitor molecules to iron atoms. Therefore, applying HIND could be an effective strategy to address corrosion-related challenges in reinforced infrastructure.