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Aconjugate containing isonicotinic acid hydrazide linked with a hydrazone bond (20 ± 2 mol%) and ionically bonded ethambutol (25 ± 2 mol%) was prepared by reacting a dialdehyde derivative of poly(galacturonic acid) successively with isonicotinic acid hydrazide and ethambutol. The obtained conjugate showed pronounced antituberculosis activity in vitro on clinical strains of M. tuberculosis and H37Rv and in vivo on Humanis and Bovis strains. The therapeutic concentrations of the active substances (isoniazid and ethambutol) in blood after administration of the conjugate to rats persisted longer than those of their low-molecular-mass analogs, thereby exhibiting a prolonged antituberculosis effect.

Взаимодействием диальдегид-производного полигалактуроновой кислоты последовательно с гидразидом изоникотиновой кислоты и этамбутолом получен конъюгат, содержащий гидразид изоникотиновой кислоты, присоединенный посредством азометиновой связи (20 ± 2 моль %), и этамбутол, присоединенный ионной связью (25 ± 2 моль %). В условиях in vitro на клинических штаммах M. tuberculosis и H37Rv, а также в условиях in vivo на штаммах Humanis и Bovis полученный конъюгат показал выраженную противотуберкулезную активность. При введении конъюгата крысам терапевтическая концентрация активных веществ (изониазида и этамбутола) в крови сохранялась дольше, чем их низкомолекулярных аналогов, что указывает на возможность пролонгирования их противотуберкулезной активности.

This research describes the formation of samarium complexation with organic ligands (Schiff bases of anti-mycobacterial agent isonicotinic acid hydrazide) through pH-metric technique at 25, 35, and 45°C in 70% (v/v) ethanol/water medium at 1M (NaClO4) ionic strength. Organic ligands have been synthesized and their structures have been confirmed by various characterization techniques such as TLC, MP, IR, 1H NMR, 13C NMR, UV-Vis spectroscopies and elemental analysis. They have been evaluated for biological activity against gram positive, gram negative bacteria, and fungi showing moderate to significant results. Complexation study of these binary complexes has been evaluated and calculated using Calvin–Bjerrum technique. The order of stability constant has been found to be as follows N-[(E)-(4-hydroxy-3-methoxyphenyl)methylene]isonicotinohydrazide (L2) < N-[(E)-(4-chlorophenyl)methylene]isonicotinohydrazide (L1) < N-[(E)-(4-hydroxyphenyl)methylen]isonicotinohydrazid (L4) < N-[(E)-(2-hydroxyphenyl)methylen]isonicotinohydrazid (L5) < N-[(E)-(2-nitrophenyl)methylen]isonicotinohydrazide (L3). Thermodynamic parameters associated with the samarium complexation have been observed to be negative in ΔH and ΔG. This indicates the exothermic reaction in complexation.

Novel isonicotinic acid hydrazide functionalized silver nanoparticles (INH-AgNPs) were synthesized by wet chemical method and used for the detection of Hg2+ ions in aqueous medium. The INH-AgNPs exhibit good absorbance and emission peaks by sensing Hg2+ ions with visible color changes. The detection of Hg2+ ions was confirmed by FT-IR, EDAX spectra and by the changing morphology of INH-AgNPs, and after addition of Hg2+ was confirmed by SEM and TEM imaging studies. Based on the emission intensity the probe INH-AgNPs exhibit a lowest detection limit (LOD) of Hg2+ to 0.18 nM. The association constant (Ka) of INH-AgNPs + Hg2+ ions is calculated using the Bensei-Hildebrand equation. Also, the probe is successfully utilized for the detection of Hg2+ ions in real water samples obtained from different fields, which showed good results.

In the article the results of studying the reaction of the interaction of isonicotinic acid hydrazide with various derivatives of aromatic aldehydes under conditions of microwave activation in an alcohol medium were described. The results of studying the dependences of the hydrazone yield on the duration of the activation time at various microwave irradiation powers in comparison with the classical method have been presented. It was found that the main factors affecting the nature of the synthesis and the yields of the target products were the power and time of microwave activation, as well as the structural features of the reactants. For all studied reactions, the optimal conditions for obtaining the target product have been shown. As a result of a comparative analysis of the results obtained for the synthesis of new isonicotinic hydrazones, it was determined that the use of microwave irradiation contributed to an increase in the yield of the product and a decrease in the reaction time by 3-4 times than according to traditional technology. The authenticity of each product is unambiguously proved by comparing the melting point, as well as by analyzing the physico-chemical characteristics with previously synthesized hydrazone derivatives of isonicotinic acid obtained by classical synthesis methods. The structure of all synthesized compounds was studied by H-1 and C-13 NMR spectroscopy, as well as data from two-dimensional COSY (H-1-H-1) spectra and HMQC (H-1-C-13). The developed microwave method for the synthesis of hydrazone derivatives of isonicotinic acid complies with the principles of the concept of "Green Chemistry".

The reaction of isonicotinic acid hydrazide with ethyl-, allyl-, and cinnamoyl isothiocyanates has afforded the corresponding alkylthiosemicarbazides and the products of their intramolecular heterocyclization, 1,2,4-triazoles.

The usual treatment for tuberculosis is difficult by its long-term therapy, raised dosing frequency and adverse effects of anti-tuberculosis drugs. Anionic clays, also called layered double hydroxides are a class of hydrotalcite like structures having high compositional variety and being able to self-assembly in the presence of drug molecules. The work refers to the development of nanohybrid materials like delivery systems that intercalates isonicotinic acid hydrazide, known as isoniazid anti-tuberculosis drug, into layered structure of hydrotalcite compounds. Loaded drug molecules of isoniazid were proved to be released in a controlled way from the as synthesized nanostructure in a simulated buffer solution. The obtained sample was characterized by advanced techniques thus demonstrating the inclusion of isoniazid antibiotic between hydrotalcite sheets. These results revealed important expectations for further researches of these organic-inorganic nanocomposites for tuberculosis treatment.

The kinetics and mechanism of the reaction of diaquacobinamide (Cbi(III)) with isoniazid (iso-nicotinoyl hydrazide (INH)) are studied. It is determined that the composition of the products depends on the ratio between the concentrations of the reactants. Adding excess INH to cobinamide results in the rapid formation of a stable complex of Cbi(III) with two isoniazid molecules. If the concentrations of isoniazid and cobinamide are close, or cobinamide is in excess, then a complex of Cbi(III) with one isoniazid molecule initially forms. There is then a fast inner-sphere electron transfer to yield an unstable complex of reduced Cbi(II) with hydrazyl radical (RN2H2)(Cbi(II)) that decomposes to form reduced cobinamide and the products of the oxidation of isoniazid: isonicotinamide, pyridine-4-carboxaldehyde, and isonicotinic acid (INA). It is concluded that with a 1000% excess of cobinamide, the main product of the oxidation of INH is INA.

The present study refers to the preparation of isonicotinic acid hydrazide (isoniazid (INH)) cocrystals with two α-hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or dl-mandelic acid (H2ma) resulted in the formation of cocrystals, or salts of composition, as isoniazid−glycolic acid cocrystal (INH)·(H2ga) (1) and isoniazid−dl-mandelic acid salt cocrystal [HINH]+[Hma]−·(H2ma) (2), when reacted with isoniazid. An N’-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pINH)·1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. The prepared compounds were well characterized by elemental analysis and spectroscopic methods, and their three-dimensional molecular structure was determined by single-crystal X-ray crystallography. Hydrogen bonds involving carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary on the basis of the steric influences of the derivative group. These are contrasted in each of the molecular systems.

Cobalt(II) and copper(II) complexes of a series (E)-N’-(5-X-salicylidene)isonicotinohydrazide Schiff bases derived from isonicotinic acid hydrazide and 5-substituted-salicylaldehydes have been synthesized and characterized by FTIR, AAS, UV-Visible spectroscopy and elemental analysis. Evaluation of the in-vitro antitubercular, antioxidant and cytotoxic activities of the compounds was carried out to establish their potential as antituberculosis agents. The FTIR spectra showed that the ligands behave as tridentate dibasic ligands towards the metal ions. The antioxidant activities of the compounds investigated through their scavenging effect on DPPH revealed that the IC50 for the nitro substituted Schiff base was highest, similarly, the LC50 value was much lower than the values for other compounds. The ligand complexes containing the nitro NO2 substituent exhibited enhanced in vitro Mycobacterium tuberculosis and antioxidant activities compared with the ligands and reference compounds (Isoniazid and vitamin C).

The tridentate Schiff base ligand o-vanillin salicylhydrazone was derived from aromatic o-vanillin and isonicotinic acid hydrazide, and its Fe(III) and Ni(II) coordination polymers ((FeHLCl2·H2O)n and (Ni2L2phen2)n, H2L = o-vanillin salicylhydrazone, phen = 1,10-phenanthroline) were prepared and fully characterized. The crystal structures of both complexes were determined by X-ray single-crystal diffraction. The interaction of the free ligand H2L and the corresponding complexes with herring sperm DNA (HS-DNA) was estimated by absorption and emission titration methods, which revealed that the compounds interacted with HS-DNA through an intercalation mode. The binding of the compounds with bovine serum albumin (BSA) protein investigated using UV-visible and fluorescence spectroscopic methods indicated that strong binding interaction exists between the complexes and BSA compared to the ligand H2L. The alterations in the secondary structure of the protein by the complexes were confirmed by synchronous fluorescence spectroscopic studies. Molecular docking calculations revealed that the complexes bind through extensive hydrogen bonding, hydrophobic and van der Waals interactions with DNA and BSA. Investigation of their antioxidative properties showed that the polymeric Ni(II) complex has a strong radical scavenging potency against nitric oxide and superoxide anion radicals. Further, in vitro cytotoxicity studies of the ligand H2L and its complexes found that the Ni(II) complex exhibited substantial anticancer activity against human lung adenocarcinoma cell lines A549 with an IC50 value of 11.67 μM, and has shown higher activity than the well-known anticancer drug cisplatin.

A simple pH fluorescent probe, N-(6-morpholino-1, 3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl) isonicotinamide (NDI), based on naphthalimide as the fluorophore and isonicotinic acid hydrazide as the reaction site was synthesized and characterized. It is useful for monitoring acidic and alkaline pH. The results of pH titration indicated that NDI exhibits obvious emission enhancement with a pKa of 4.50 and linear response to small pH fluctuations within the acidic range of 3.00–6.50. Interestingly, NDI also displayed strong pH-dependent characteristics with pKa 9.34 and linearly responded to an alkaline range of 8.30–10.50. The sensing response mechanism was confirmed by 1H NMR and ESI-MS spectroscopy. The mechanism of the optical responses of NDI toward pH was also determined by density functional theory (DFT) calculations. In addition, NDI displayed a highly selective and sensitive response to hydrogen ions and hydroxyl ions. The probe was successfully applied to image acidic and alkaline pH value fluctuations in HeLa cells and has lysosomal targeting ability.

A new calcium(II) complex was synthesized by one-pot synthesis method from disodium 4-formylbenzene-1,3-disulfonate, isonicotinic acid hydrazide and Ca(ClO 4 ) 2 • 2H 2 O. The structure of calcium(II) complex was determined by elemental analysis, IR and single crystal X-ray diffraction. The results show that the Ca(II) complex molecules form 3D network structure by the interactions of π-π stacking and hydrogen bonds. The Ca(II) complex catalyst could efficiently catalyse oxidation of benzylic alcohol with good conversion of benzyl alcohol (78 %) and excellent selectivity of benzaldehyde (98 %). Copyright © 201 8 BCREC Group . All rights reserved . Received: 13rd December 2017; Revised: 23rd May 2018; Accepted: 23rd May 2018 How to Cite : Tai, X.S., Li, P.F., Liu, L.L. (2018). Synthesis, Crystal Structure, and Catalytic Activity of a Calcium(II) Complex with 4-Formylbenzene-1,3-disulfonate-isonicotinic Acid Hydrazone. Bulletin of Chemical Reaction Engineering & Catalysis , 13 (3): 429-435 (doi:10.9767/bcrec.13.3.1961.429-435) Permalink/DOI : https://doi.org/10.9767/bcrec.13.3.1961.429-435

New pyridine derivatives were designed and synthesized as Isonicotinic acid hydrazide (INH) analogues. The synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis strain H37Rv. Ten compounds (3c, 3e-g, 5a-c, 6h, 10 and 11b) showed promising antitubercular activity with MIC range 7.30 µM–19.39 µM. Compounds 3e, 3g, 5b and 11b were the most potent analogues, with MIC 7.30–8.74 µM. They were equipotent to the standard drug Ethambutol (MIC 7.64 µM) and more active than the standard drug Pyrazinamide (MIC 50.77 µM). They were further examined for cytotoxicity in human embryonic kidney (HEK) cell line at the concentration of 50 µg/mL using MTT assay. Results declared that most compounds showed acceptable safety margin. Molecular Docking studies into 2-trans-enoyl-acyl carrier protein reductase, called InhA have been conducted for compounds 3e, 3g, 5b and 11b using Molecular Operating Enviroment software (MOE 2016.0802), where reasonable binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration and Osiris software.

Trifluoromethylation of isonicotinic acid hydrazide has been investigated in trifluoroacetic acid containing pyridine, triethylamine and sodium trifluoroacetate dissolved in acetonitrile on platinum and glassy carbon electrodes using cyclic voltammetry. LSVs for isonicotinic acid hydrazide in 0.1 M TFA/ Py/TEA/NaTFA in acetonitrile on platinum electrode show that there is no distinct oxidation peak for the oxidation of isonicotinicacid hydrazide within the voltammetric region of 0.0 to 1.6 V vs Ag and it gets oxidized anodically in the gas evolution region itself. TFA/ NaTFA medium shows slightly higher current density than the other two media for the oxidation of isonicotinic acid hydrazide. CVs for different concentrations of isonicotinic acid hydrazide show that anodic peak becomes broad and flat. It shows that severe adsorption of INAH/product takes place on the glassy carbon electrode during the voltammetry scanning. Galvanostatic electrolysis of INAH in TFA/Py/ACN medium at low current density on Pt shows good conversion with low selectivity.

Liposomes are considered as potential vehicles for the delivery of anti-tuberculosis drugs (ATBD) due to their rapid uptake by alveolar macrophages, where the mycobacterium often resides. This may provide macrophage-targeting effects that would be key to site specific ATBD delivery using pH-sensitive liposomes, considering the pH-gradient found in the phagocytotic pathway. In this study, isoniazid (INH) was conjugated to 4-hydroxy-benzaldehyde via a hydrazone bond to yield isonicotinic acid (4-hydroxy-benzylidene)-hydrazide (INH-HB). This conjugate was encapsulated in crude soybean lecithin liposomes using film hydration method. INH-HB loaded liposomes (IHL) were characterized by means of dynamic light scattering, transmission electron microscopy, differential scanning calorimetry and X-ray diffraction. The release of INH from IHL was evaluated in media of different pH using a dialysis method. The particle size, Zeta Potential and encapsulation efficiency of IHL were about 945 nm, −62 mV and 89% respectively. In media of pH 7.4, 6.4, 5.4 and 4.4; the IHL exhibited respectively 22, 69, 83 and 100% of release over 12 h. In addition to possible targeted delivery, this pH-dependent release behavior may be suitable for minimizing the loss of INH by leakage from liposomes. The characteristics of IHL are promising for potential site-specific delivery of ATBD.

Due to growing resistance and continuous colonization among microbes, researchers are eager to design and put forth antibiotic substances of effective anti-nosocomial infection activity. Under such purview, the current report deals with synthesis and formulation of a dioxomolybdenum(VI) complex of general formula [MoO2(L)(H2O)], where H2L = N-(o-hydroxyacetophenone)isonicotinic acid hydrazide (H2haina), as antibiotic compound against hospital acquired infections. The complex was characterized by elemental analysis, conductance determination, magnetic susceptibility measurements, Proton Nuclear Magnetic reonance spectroscopy (1HNMR), Fourier-transform Infra-red spectroscopy (FTIR), mass spectrometry, thermal and electronic spectral studies. Experimental data results were compared with theoretical outcomes by invoking density functional theory-based molecular topography and conjoint spectroscopic analysis with the help of Gaussian09 software package using LANL2DZ/B3LYP combination for the cis-dioxo group of distorted octahedral complex, [MoO2(haina)(H2O)]. The experimental and theoretical outcomes were found in an excellent agreement with one another. The overall study reveals that the complex under investigation possesses a cis-dioxo-octahedral geometry. Significant antimicrobial activity of the complex was obtained against hospital origin microbes in comparison with some selected standard commercial drugs including tetracycline and azithromycin. E. Coli and Pseudomonas were the microbes selected for the study.

The problem of designing new antitubercular drugs against multiple drug‐resistant tuberculosis (MDR‐TB) was addressed using advanced machine learning methods. As there are only few published measurements against MDR‐TB, we collected a large literature data set and developed models against the non‐resistant H37Rv strain. The predictive accuracy of these models had a coefficient of determination q2=.7–.8 (regression models) and balanced accuracies of about 80% (classification models) with cross‐validation and independent test sets. The models were applied to screen a virtual chemical library, which was designed to have MDR‐TB activity. The seven most promising compounds were identified, synthesized and tested. All of them showed activity against the H37Rv strain, and three molecules demonstrated activity against the MDR‐TB strain. The docking analysis indicated that the discovered molecules could bind enoyl reductase, InhA, which is required in mycobacterial cell wall development. The models are freely available online (http://ochem.eu/article/103868) and can be used to predict potential anti‐TB activity of new chemicals.

This study describes the synthesis, lipophilicity and in vitro antimicrobial assays of 15 new hydrazide-hydrazones of isonicotinic acid. New derivatives were obtained on the basis of the condensation reaction of isonicotinic acid hydrazide with different aromatic aldehydes. The chemical structure of synthesized compounds was confirmed by spectral methods. Experimental lipophilicity of new isonicotinic acid derivatives was determined using reversed-phase thin-layer chromatography. All synthesized compounds were subjected to in vitro antimicrobial assays against reference strains of Gram-positive bacteria, Gram-negative bacteria and fungi belonging to Candida spp. Some of the synthesized hydrazide-hydrazones proved to be significant antibacterial compounds and more potent than commonly used chemotherapeutic agents.

The {[Cu2Ge(μ-Cit)2(μ-INH)2]·4H2O} n (I) complex, where H4Cit is citric acid, INH is isonicotinic acid hydrazide, is synthesized for the first time and characterized by a set of physical and chemical analysis techniques. According to X-ray crystallography, I is a three-dimensional heteronuclear Cu–Ge coordination polymer with a completely deprotonated form Cit4– of citric acid. Both ligands are bridging and the framework structure of the complex is formed.

Introduction: Epilepsy is a chronic neurological disorder, involving group of nerve cells, or neurons, in the brain. Many classes of antiepileptic drugs are being prescribed and used by the stake holders but most of them are associated with serious side effects and toxicity. There is a strong need of new antiepileptic molecules with less side effects and toxicity. Objective: A series of aryl acid hydrazones of Isonicotinic acid hydrazide (RINH1 -RINH14) were synthesized and evaluated for Anticonvulsant activity. Material and Method: Compounds (RINH1 -RINH14) were synthesized by refluxing Isonicotinic acid hydrazide with different substituted benzaldehydes/ substituted acetophenones in absolute ethanol. Melting points of all synthesized compounds were monitored by open glass-capillary tube method on Digital Melting point apparatus and are uncorrected. The synthesized compounds were tested for anticonvulsant potential using MES and scPTZ whereas neurotoxicity was determined using Rotarod model. Result and Discussion: At 100mg/kg compound RINH10 have shown 29% protection at both 0.5hr and 4.0 time interval .At 300mg/kg and 0.5 hr, compounds RINH4 and RINH10 showed 100% and 50 % protection respectively. Compounds RINH4 and RINH10 have better anti MES activity proving that halogens have prominent contribution in Anticonvulsant activity. In scPTZ screen, all synthesized Acid hydrazone (RINH1- RINH14 ) did not show any protection at 30, 100,300 mg/kg , at 0.5 hr and 4.0 hr duration .In rotorod test i.e neurotoxicity screen, compound RINH5, RINH6 , RINH10 have shown toxicity. Conclusion: The synthesized new molecules were proved to be having anticonvulsant activity with less signs of neurotoxicity.

Through functionalizing of isonicotinic acid hydrazide (INAH) on to fumed silica nanoparticles, a novel fluorescent nanomaterial (fumed-Si–INAH) was synthesized and characterized using various techniques including FT-IR, SEM, and TGA. Next, interaction of the new nanofluorophore material with metal cations was studied spectrofluorimetrically. The fluorescence evaluation of fumed-Si–INAH towards a wide range of cations including Pb2+, Cd2+, Zn2+, Cu2+, Fe2+, Ca2+, Ni2+, Mn2+, Mg2+, Co2+, Na+, Hg2+, Cr3+, and K+ revealed that fumed-Si–INAH was a highly selective optical sensor for Hg2+ and Cr3+ ions in a wide range of pH in water. Thus, it was applied as a fluorescent bulk sensor for Hg2+ and Cr3+ ions. The detection limits were obtained to be 3.5 × 10−5 and 4.2 × 10−5 M for Hg2+ and Cr3+, respectively.

Kinetics of the reaction of aquacobalamin (H2OCbl) with isoniazid (isonicotinic acid hydrazide, INH) in weakly alkaline, neutral, and weakly acidic media was studied using UV–Vis spectroscopy. It is shown that the reversible formation of a complex more stable than those of cobalamin(III) with pyridine and hydrazine occurs during the reaction. A mechanism of the reaction includes reversible stages of binding a neutral INH molecule by cobalamin(III) through an oxygen atom with its subsequent deprotonation, along with the reversible interaction of H2OCbl and the negatively charged form of INH.

Metal–organic films onto the solid surface have been successfully assembled through Layer-by-Layer (LbL) deposition methods. The organic ligand isonicotinic acid (3-pyridylmethylene) hydrazide containing pyridine groups was chosen to act as a useful building unit, and K2PdCl4 was used as the precursor for the films preparation. UV–vis spectra, transmission electron microscopy (TEM), atomic force microscopy (AFM), and inductively coupled plasma optical emission spectrometry (ICP-OES) were applied to understand the growth process of the resulting LbL multilayers. The LbL films with 10 layers (denoted as (Pd-ligand)10) were further applied as catalysts for the hydrogenation of nitroarenes. It is worth mentioning that our films catalyst is convenient to recycle and possesses good reusability.

We studied the response of the extracellular matrix of the lungs and liver in mice with BCGinduced granulomatosis (3 months) after inhalation and intraperitoneal administration of liposome-encapsulated dextrazide (LEDZ): a conjugate of oxidized dextran (40 kDa) and isonicotinic acid hydrazide (INH). LEDZ inhalation proved to be more effective in reducing fibrosis severity, both in the lungs and liver. However, the mechanisms of the antifibrotic effect were different: increased degradation and reduced collagen synthesis in the lungs and reduced collagen synthesis and collagen degradation in the liver. This suggest that drug administration routes and delivery to the target organs are crucially important in the therapy of tuberculosis. The antifibrotic effect depended on LEDZ administration route and was more potent after LEDZ inhalation.

Remodeling of the extracellular matrix of the liver in mice with BCG-induced granulomatosis after 2-month course of intraperitoneal injections of isonicotinic acid hydrazide, oxidized dextran conjugated with isonicotinic acid hydrazide, dextrazide, and its liposome-encapsulated form manifested in modification of the proteoglycan composition and hydroxyproline fractions associated with changes in hyaluronidase and MMP activities. The antifibrotic effect of dextrazide and its liposome-encapsulated form manifested in reduction of hydroxyproline fractions that reflected the process of collagen synthesis. Administration of isonicotinic acid hydrazide was followed by a decrease in hydroxyproline fractions reflecting collagen synthesis (antifibrotics effect) and degradation (profibrotic effect), which can be explained by its hepatotoxic activity.

In the present study, two new series of pyrazolines (3a–h & 4a–h) were synthesized starting from p-acetamidophenol (paracetamol) and evaluated for their antibacterial, antifungal and antitubercular activities. Chalcones (2a–h) prepared by condensing 3-acetyl-4-hydroxyphenyl acetamide (1) with different aromatic aldehydes were reacted with phenyl hydrazine and isonicotinic acid hydrazide to obtain phenyl-pyrazolines (3a–h) and isoniazid-pyrazolines (4a–h), respectively. The structures of the synthesized compounds were confirmed by spectral and microanalysis studies. Newly prepared pyrazoline compounds exhibited significant antibacterial activity against the organisms Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa when compared with the standard antibiotic Ciprofloxacin. Compound 4g showed potent antibacterial activity against P. aeruginosa and S. aureus (MIC-3.12 μg/mL), however, against E. coli compound 3d, 4c, 4d, 4f & 4g were found to have an MIC of 6.25 μg/mL. Antifungal activity of compound 4d against Candida albicans and Aspergillus niger (MIC-3.12 μg/mL) was found to be better than the standard drug Ketoconazole. The results of antitubercular activity of the synthesized compounds against Mycobacterium tuberculosis H37Rv by the agar microdilution method are quite promising. The antitubercular activity of compounds 4c, 4d & 4g (MIC-3.12 μg/mL) was found to be superior than that of the reference drug Streptomycin which showed MIC equal to 6.25 μg/mL. It was observed that pyrazolines with chloro, nitro or methoxy substituent showed better activity. Also, the pyrazolines derived from isoniazid (4a–h) were found to be better in their antibacterial, antifungal and antitubercular action than those derived from phenyl-hydrazine (3a–h).

Проведено исследование острой токсичности противотуберкулезной фармацевтической субстанции – конъюгата полиальдегиддекстрана с гидразидом изоникотиновой кислоты (декстразид). Исследования проводились на животных и культурах клеток линий HepaRG и фибробластах кожи человека FRSN. В результате исследования были определенны среднепереносимые (ЛД10, ЛД16), среднесмертельные (ЛД50) и летальные (ЛД84) дозы декстразида при внутрибрюшинном введении мышам и крысам и при внутривенном введении кроликам.

The synthesis of N-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)] methylisatins has been performed by the addition of isatin and 5-butylisatin to the double bond of dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidene)methylphosphonate. Subsequent functionalization of the compounds synthesized with thiosemicarbazide hydrochloride, 3-(3′,5′-di-tert-butyl-4′-hydroxyphenyl)propionic acid hydrazide, and isonicotinic acid. Hydrazide gave isatin derivatives containing several pharmacophore fragments. Each of them has the ability to the increase the antioxidant and biological activities of these compounds.

Optically active isoniazid derivatives containing a cyclopropane or cyclobutane fragment have been synthesized by ozonolysis of (+)-Δ3-carene and (–)-α-pinene, followed by treatment of the ozonolysis products with isonicotinic acid hydrazide.

Nano-sized electrodes have their special advantages for sensing applications, such as small overall dimension, fast response and low background current. In this work, single gold nanoclusters (AuNCs) were controllably prepared on single Pt nanoelectrode surface by electrodeposition method. The AuNCs covered Pt nanoelectrode (AuNCs/PtNE) had steady-state voltammetric response in redox species solution, which was similar to micro-/nano-sized electrodes. It was interesting to find isonicotinic acid hydrazide (INH, also known as isoniazid) showed good electrochemical response on AuNCs/PtNE surface, which had investigated carefully by square wave voltammetry (SWV) and chronoamperometry. Moreover, the prepared single AuNCs/PtNEs showed the capability for INH sensing with good sensitivity, reproducibility and selectivity, which was demonstrated for INH detection in human urine samples.

Besides physicochemical properties, careful design of biomolecular surface corona can dictate therapeutic potential of nanoparticles. Therefore, we demonstrate a new approach to improve the anticancer potential of gold nanoparticles (AuNPs) by developing a strong corona of curcumin and isonicotinic acid hydrazide (INH) around them. Here, curcumin reduced AuNPsCur are surface-functionalized with biologically active INH (AuNPsCur@INH). Our investigations on human lung squamous carcinoma (LK-2) and human lung fibroblast (TIG-120) cells indicate selective toxicity of functionalized nanoparticles. Conjugation of curcumin and INH on the surface of AuNPs induced anticancer action through reactive oxygen species (ROS) generation. The further extension of this study revealed apoptosis and morphological changes in LK-2 and TIG-120 cells, respectively. Moreover, the anticancer potential of these nanoparticles is compared with standard cisplatin. The outcomes of the work determine that the facile functional surfaces on nanoparticles can be important in controlling the biological activities of nanoparticles.

The reaction between 2,5-hexanedione and isonicotinic acid hydrazide in EtOH gave two products. The ethanol insoluble product was identified as 2,5-hexanedione bis(isonicotinylhydrazone) [HINH] and the soluble ethanol product as N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide [DINA]. A series of Cr(3+), Fe(3+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Pd(2+) complexes of HINH and Co(2+), Cu(2+), Zn(2+) and Hg(2+) complexes of DINA have been synthesized and structurally characterized. Based on the elemental analysis, mass spectra and molar conductance, the complexes have assigned the proposed imperical formulae. The crystal structures of N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide and its Zn(2+) and Hg(2+) complexes have been solved by X-ray diffraction having [Zn(DINA)2Cl2] and [Hg(DINA)2Cl2] in a tetrahedral structure. In the DINH complexes, the ligand coordinates as a monodentate through the pyridine nitrogen. On the other hand, HINH behaves as a tetradentate (neutral or binegative) manner with the two metal ions. The magnetic moments and electronic spectra of all complexes provide tetrahedral, square-planar, trigonal biyramid and/or octahedral structure. The thermal decomposition of the complexes revealed the outer and inner solvents as well as the end product. The steady part of [Zn(DINA)2Cl2] and [Hg(DINA)2Cl2] thermograms till 303 and 286 °C indicates the absence of any outside solvents. All compounds have activity against bacteria more than fungi. [Cd4(HINH)Cl8]·3H2O has the highest values.

Complexes of cobalt(II), nickel(II), and zinc(II) valerates and benzoates with isonicotinic acid hydrazide (isonicotinic hydrazide) have been synthesized. The prepared compounds have been characterized by means of elemental analysis, thermogravimetry, and IR and diffuse reflectance spectroscopy.

The literature survey reveals that pyrazoline derivatives have been studied extensively because of their ready accessibility, diverse chemical reactivity, broad spectrum of biological activity and variety of Industrial applications. Pyrazolines with sulphonamidoaryl substituent at 3-position show cerebroprotective, antidepressant activity , anti-implantation activity, hypoglycemic activity. Due to this vital biological roll of pyrazoline derivatives it was thought to synthesized titled pyrazolines. 2-Acetyl-1-naphthol is prepared by Modified Nenchi’s method which on treatment with furfuraldehyde and KOH gives 1-(1-hydroxy naphthalen-2-yl)-3-(furan-2-yl) prop-2-ene-1-ones in excellent yield. The chalcone when subjected to hydrazine / phenyl hydrazine/ semicarbazide / 2,4 dinitro phenyl hydrazine / isonicotinic acid hydrazide in DMF solvent to gives 3-(1-hydroxy naphthalene-2-yl)-5-(furan-2-yl)-1-substituted pyrazolines in 35-45% yield. All the melting points were taken in silicon oil bath with open capillary tubes and are uncorrected. 1 H NMR spectra were recorded on a Brucker AC300 FNMR spectrometer (300MHz), using TMS as an internal standard. IR spectra were recorded on a Nicolet-Impact 400 FT-IR spectrometer. Thin Layer Chromatography on silica gel-G, was used to check the purity of the compounds. Microanalysis of nitrogen was obtained on Colman 29-N analyzer. The synthesized compounds were characterized by elemental analysis, 1H NMR, IR Spectroscopy. All Newly synthesized compound were scanned for their antimicrobial and antifungal activity and all newly synthesized compounds shows an excellent antimicrobial and antifungal activities.

A Schiff base ligand was synthesized from the reaction of isonicotinic acid hydrazide with 3-methoxysalicylaldehyde. The reaction of LH with Co(NO3)2 .6H2O in methanol gave dark red crystals of [Co(HL)2](NO3)2.3H2O and colorless crystals of the protonated ligand (HLH)+ with nitrate as the counter ion, (HLH)(NO3). In coordination to metal, Schiff base ligand was protonated via hetrocyclic nitrogen atom of the pyridine ring and deprotonated on the phenolic OH group, two ligands behave as neutral tridentate ligands. The extensive O–H···O and N–H···O hydrogen bonding interactions in the solid state contribute to the formation of an infinite one-dimensional chain in the complex.

The pharmacokinetics of the promising antituberculosis drug dextrazide, the conjugate of polyaldehyde dextran with isonicotinic acid hydrazide, were studied using outbred ICR mice. The obtained results were indicative of two-phase dextrazide pharmacokinetics.

Hsp90, as a key molecular chaperone, plays an important role in modulating the activity of many cell signaling proteins and is an attractive target for anticancer therapeutics. Herein, we report the discovery of N-pyridoyl-Δ2 -pyrazoline analogs as novel Hsp90 inhibitors by integrated approaches of drug design, organic synthesis, cell biology, and qualitative proteomic analysis. Novel chemical compounds were designed and optimized in the adenosine triphosphate-binding site of Hsp90; lead optimized compounds were found to have significant interactions with Asp93 and other amino acids crucial for Hsp90 inhibition. The designed compounds were synthesized by a two-step procedure; different aromatic aldehydes were reacted with various acetophenones to form substituted 1,3-diphenyl-prop-2-enones (Ic-Io), which upon reaction with isonicotinic acid hydrazide in the presence of glacial acetic acid form N-pyridoyl-Δ2 -pyrazoline compounds (PY1-PY13). Compounds PY3, PY2, and PY1 were identified as potential leads amongst the series, with promising anticancer activity against human breast cancer and melanoma cells, and the ability to inhibit Hsp90 similar to radicicol by drug-affinity responsive target stability proteomic analysis in a whole-cell assay.

Crystallization of three diterpenoid isosteviol derivatives with a structural fragment of isoniazid (isonicotinic acid hydrazide) and its isomers – hydrazides of nicotinic and picolinic acids (structures 5, 6 and 7 respectively) was studied by single-crystal and powder XRD. These homochiral compounds crystallize in “Sohnke” space group P21 with two independent molecules. In crystals 5 and 6, an infinite H-bonded chain of alternating molecules A and B formed by N–H⋯OC interaction is observed, while only pairwise the same interactions between molecules A and B are realized in crystal 7. In the H-bonded associates of both types, the local (non-crystallographic) mirror-symmetry of nitrogen containing substituents in molecules A and B is observed. Such type of crystal packing – H-bonded chains or dimers formed by the N–H⋯OC interaction through the glide plane – is the most typical packing in achiral compounds with a structural fragment of isoniazid and its isomers, as the CCDC analysis showed. Thus, structures 5–7 represent an interesting example of transferring a robust supramolecular mirror-symmetry motive from a racemic environment into a homochiral one, but inclusion of an “extra” molecule in a unit cell is the crystallographic “cost” of such transfer.

Condensation of methyl N-(4-acetylphenyl)carbamate with aromatic aldehydes in basic and acid environment, and also with hetarylaldehydes in the presence of bases afforded chalcones with the carbamate function. Under the conditions of basic catalysis a nucleophilic substitution was observed of a methoxy group in the carbamate moiety of the chalcone for an ethoxy group. The reactions of the obtained chalcones with hydrazine hydrate, isonicotinic acid hydrazide, guanidine and hydroxylamine hydrochlorides, thiourea, and selenium dioxide furnished the corresponding derivatives of pyrazole, oxazole, pyrimidine, and selenadiazole.

Metal semicarbazone and thiosemicarbazone complexes have attracted much attention due to their diverse biological activities. Because of the ability of ruthenium(II)-arene species to coordinate to different classes of ligands, they are suitable for fine-tuning chemical and pharmaceutical properties. Ruthenium(II) arene-complexes containing different types of ligands: namely caprylic hydrazide (a hydrazide with a long hydrocarbon chain), isonicotinic acid hydrazide (a hydrazide with an aromatic pyridine ring), thiosemicarbazones and semicarbazones (derived from the reaction of 3- and 4-acetylpyridine with either thiosemicarbazide or caprylic hydrazide), were obtained in the reaction of [(eta(6)-p-cymene)RuCl2](2) with the corresponding ligands in a 1:2 or 1:2.2 molar ratio in methanol, ethanol or isopropanol with mild heating. The complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies. The structure of complex 1 was determined by X-ray crystallography. Antiproliferative activity of the investigated complexes, determined for three human cancer cell lines (HeLa, A549 and LS-174) revealed moderate activity without significant influence on the matrix metalloproteinases (MMP-2 and MMP-9) activity.

Enoyl–acyl carrier protein reductase (InhA) is an important enzyme for the biosynthesis of mycolic acids which are central constituents of the mycobacterium cell wall. In the present study, we synthesized, characterized hydrophobic N-acylated isonicotinic acid hydrazide derivatives (2a–2m) as potential enoyl–acyl carrier protein reductase (InhA) inhibitors and tested them against Mycobacterium tuberculosis H37Rv and two human clinical isolates by means of colorimetric tetrazolium micro-plate assay. Compounds 2c–2m displayed good-to-excellent inhibitory activity against all tested strains as compared with isoniazid. In vivo acute toxicity studies were performed by Up-and-Down procedure. The results showed that all the tested compounds were non-toxic and well tolerated considering their LD50 values ranging from 3,898 to 5,000 mg/kg body weight.

The isonicotinoylhydrazones and their coordination compounds have antibacterial, antifungal, antitubercular, antitumor, and anticonvulsant activities. A typical method employed in the preparation of isonicotinoylhydrazones involves the usage of the volatile organic solvents during the condensation reaction between isonicotinic acid hydrazide and carbonyl compounds. It has been shown that the solvent-free technique can be applied to obtain crystalline compounds. Reaction of isoniazid with carbonyl compound under solvent-free conditions results in microcrystalline solid state isonicotinoylhydrazones. The influence of solvent effect on the mechanism of condensation reaction was evaluated and the most significant intermediates and transition states, in the gas phase and in the presence of water and methanol were resolved. The solvent has positive effect on the reaction mechanism, but the organic solvent is unnecessary during the synthesis of crystalline isonicotinoylhydrazones derived from aldehydes. Mixing s...

A mononuclear dioxo vanadium(V) complex of a hydrazone ONO donor ligand, [VVO2(L1)] (1), was synthesized by the reaction of V2O5 and terephthalic acid with H2L1 in 1:1:1 mol ratio, while an oxo-bridged bis(vanadium(IV)oxo) complex, [μ 2–O–{VIVO(L2)}2] (2), was synthesized by the treatment of isonicotinic acid hydrazide, salicylaldehyde and CoSO4·7H2O with bis(acetylacetonato)oxovanadium(IV) (H2L1 = isonicotinic acid(2-hydroxy-benzylidene)-hydrazide, H2L2 = isonicotinic acid (1-methyl-3-oxo-butylidene)-hydrazide). The complexes were characterized by elemental analyses and spectroscopic methods. The crystal structure of complex 2 was determined by X-ray analysis. The complexes were tested as catalysts for the oxidation of cycloalkenes and benzyl alcohol using H2O2 as terminal oxidant. Excellent selectivity was achieved in the oxidation of cyclohexene.

The present work reports an efficient synthesis of fluorinated pyridinium salts-based hydrazones under both conventional and eco-friendly ultrasound procedures. The synthetic approach first involves the preparation of halogenated pyridinium salts through the condensation of isonicotinic acid hydrazide (1) with p-fluorobenzaldehyde (2) followed by the nucleophilic alkylation of the resulting N-(4-fluorobenzylidene)isonicotinohydrazide (3) with a different alkyl iodide. The iodide counteranion of 5-10 was subjected to an anion exchange metathesis reaction in the presence of an excess of the appropriate metal salts to afford a new series of fluorinated pyridinium salts tethering a hydrazone linkage 11-40. Ultrasound irradiation led to higher yields in considerably less time than the conventional methods. The newly synthesized ILs were well-characterized with FT-IR, ¹H NMR, (13)C NMR, (11)B, (19)F, (31)P and mass spectral analyses. The ILs were also screened for their antimicrobial and antitumor activities. Within the series, the salts tethering fluorinated counter anions 11-13, 21-23, 31-33 and 36-38 were found to be more potent against all bacterial and fungal strains at MIC 4-8 µg/mL. The in vitro antiproliferative activity was also investigated against four tumor cell lines (human ductal breast epithelial tumor T47D, human breast adenocarcinoma MCF-7, human epithelial carcinoma HeLa and human epithelial colorectal adenocarcinoma Caco-2) using the MTT assay, which revealed that promising antitumor activity was exhibited by compounds 5, 12 and 14.

A series of N(2)-acyl isonicotinic acid hydrazides (1-17) was synthesized and tested for its in vitro antimycobacterial activity against Mycobacterium tuberculosis and the results indicated that the compound, isonicotinic acid N'- tetradecanoyl-hydrazide (12) was more active than the reference compound isoniazid. The results of antimicrobial activity of the synthesized compounds against S. aureus, B. subtilis, E. coli, C. albicans and A. niger indicated that compounds with dichloro, hydroxyl, tri-iodo and N(2)-tetradecanoyl substituent were the most active ones. The antiviral activity studies depicted that none of the tested compounds were active against DNA or RNA viruses. The multi-target QSAR model was found to be effective in describing the antimicrobial activity of N(2)-acyl isonicotinic acid hydrazides.