Isoniazid Research Articles

Synthesis and Characterization of Some Oxazolidine and Thiazolidine Derivatives and Study of their Antioxidants Activity

In this work, the preparation of some new oxazolidine and thiazolidine derivatives has been conducted. This was done over two steps; the first step included the synthesis of Schiff bases A1-A5 in 72-88% yields by the condensation of isonicotinic acid hydrazide and aldehydes. The second step includes the cyclization of derivatives A1-A5 with glycolic acid and thioglycolic acid to obtain the desired products, oxazolidine derivatives B1-B5 (44-60% yields) and thiazolidine derivatives C1-C5 (41-61% yields), respectively. The structure of the prepared compounds was characterized using FT-IR, 1H NMR, and 13C NMR spectroscopy. Some of the produced compounds were tested for antioxidant properties.

Chemotherapy Options in New Patients with Drug Susceptible Tuberculosis and Concurrent HIV Infection

The objective: to compare effectiveness and safety of isonicotinoylhydrazine-O,N' iron (II) sulfate dihydrate with the drug of isonicotinic acid hydrazide group in the complex therapy of patients with drug susceptible tuberculosis and HIV infection.Subjects and Methods. In 2020-2021, 40 patients with HIV infection and drug susceptible respiratory tuberculosis with a positive sputum test were examined in Moscow Regional Clinical TB Dispensary as a part of the post-registration observational study. The subjects were randomized into two groups – Main Group (MG) and Comparison Group (CG). Isonicotinoylhydrazine-O,N' iron (II) sulfate dihydrate was administered to the patients from MG as a part of regimen 1 of chemotherapy (instead of isoniazid). The effectiveness and safety of the investigational drug and comparator were evaluated. The primary effectiveness criteria included resolution of clinical symptoms of intoxication and sputum conversion. The secondary effectiveness criterion was positive X-ray changes. The safety criterion was the absence of adverse reactions.Results. During the study period, no adverse reactions were registered when isonicotinoylhydrazine-O,N' iron (II) sulfate dehydrate was used, as well as isoniazid. Good tolerability was noted as well as high compliance to treatment by patients. Thus, both in terms of effectiveness and safety, isonicotinoylhydrazine-O,N' iron (II) sulfate dihydrate is comparable to isoniazid as part of anti-tuberculosis chemotherapy for patients with drug susceptible tuberculosis and concurrent HIV infection.

Understanding Isoniazid Crystals Agglomeration Through Quality by Design and Artificial Neural Network Analysis

Introduction: The aims of this study were to determine and govern critical sources of variability in the process and to investigate the effect of excipients and processing conditions on the critical quality attributes (CQAs) of isoniazid (INZ) crystal agglomerates using a quality-bydesign (QbD) paradigm along with risk-based approach. Methods: The QbD paradigm is thoroughly exercised to determine the CQAs and to, link these CQAs to agglomerate properties and to recognize potentially significant input variables. Considering this, a risk assessment tool was executed with different excipients and processing conditions to define their effect on CQAs of agglomerates. Potential risk factors were recognized using an Ishikawa diagram and then investigated using principal component analysis and an artificial neural network. After that, all agglomerates were optimized using the design of the experiment. Results: The optimized INZ crystal agglomerates were characterized using various tools such as X-ray diffractometry, Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, gas chromatography, and stability testing. These characterizations confirmed that INZ did not undergo any structural modifications in the agglomerates. Conclusion: The results indicate that the QbD principles and risk assessment tool provide a valuable means to fully understand directly compressible INZ crystal agglomerates, which could be considered an exceptional alternative to the granulation method.

Adsorption Effects of Isoniazid Drug Over Carbon Nanotube (C56H16) and Ab‐Initio Molecular Dynamics Simulation (ADMP) – A Computational Quantum Chemical Approach

AbstractTuberculosis (TB) is a deadly disease of global concern. The previous work studies the geometric optimization, vibrational analysis, TDDFT, and electronic properties of the TB pathogen drug isoniazid (ISO). This communication will discuss the changes in geometry, electronic properties, and shielding parameters of ISO‐absorbed carbon nanotube (CNT) (CNT‐ISO, C56H16). This study has used the DFT/B3LYP/6–311G (d, p) method for the first time to report ISO's electronic structure and interaction parameters on the CNT surface. The same level theory is used to discuss the thermodynamic stability of CNT‐ISO. The calculated UV spectra of CNT are compared with UV spectra of CNT‐ISO by using the same level theory in a water solvent, which provides a better comprehension of CNT as a drug delivery system after absorption of the ISO in the human body. The nature and strength of interactions have been discussed with the help of NBO and AIM analysis, and the frontier orbital highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO‐LUMO) gap, chemical softness, and chemical hardness have been calculated to understand its complete chemical properties. The characters of the frontier molecular orbitals are discussed and analyzed by comparing the DOS spectra of CNT with CNT‐ISO. It has also examined the scan plot of interaction with time using ab‐initio dynamics simulation (ADMP) calculations.

The isoniazid drug adsorption on the boron carbide graphene-like monolayer: insights from simulation in the field of medicine

To determine the electrical sensitivity of BC3 nanosheets to isoniazid (IS), DFT simulations were performed. IS molecules were found to have a clear affinity for pure BC3. The adsorption energy of the most stable structure is approximately −22.12 kcal/mol. Reducing the gap between the HOMO and LUMO levels of BC3 nanosheets significantly (from 1.45 to 0.72 V) enhances IS adsorption and consequently improves the electrical conductivity. This finding positions BC3 as a viable choice for applications like IS detection and electronic sensors. Moreover, the adsorption of IS has altered the work function of BC3, suggesting its potential as a function-based sensor capable of detecting IS through significant shifts in field electron emission current levels. BC3 also offers the advantage of rapid IS desorption, with a recovery time of approximately 6.18 ms.

The role of phenotypic factors in predicting the effectiveness of chemoprophylaxis in children

Background. The purpose was to study the prognostic role of some phenotypic factors in the effectiveness of tuberculosis chemoprophylaxis in children at present stage. Materials and methods. To study the role of phenotypic factors in predic­ting the effectiveness of tuberculosis chemoprophylaxis, an analysis was performed of dermatoglyphic indicators, gender, and the inactivation phenotype of isonicotinic acid hydrazide (IAH) in 76 children with tuberculin skin test conversion who underwent a 3-month course of preventive therapy with isoniazid. Dermatoglyphics of fingers and palms was determined according to the standard method [5]. The dynamics of skin sensitivity to tuberculin PPD-L according to the Mantoux test with 2 tuberculin units was used as a criterion for the effectiveness of chemoprophylaxis. According to the latter, the examinees were divided into two groups: the first one consisted of 52 children in whom the size of a wheal decreased by 4 mm or more after the end of a course (effective chemoprevention); the second one included 24 patients in whom skin sensitivity to tuberculin increased or remained at the previous level or decreased by a wheal size for 3 mm or less (ineffective chemoprevention). Results. The conducted statistical analysis revealed a significant difference in 7 indicators between the groups (p < 0.05). Determination of their prognostic informativeness made it possible to rank the prognostic significance of phenotypic signs, namely: the size of the atd angle on the left palm (J = 1.7), the number of ulnar loops on the right hand (J = 1.4), the type of IAH inactivation (J = 1.3), the number of whorls on the right hand (J = 1.2), the total number of whorls (J = 1.1), the atd angle on the right palm (J = 0.7), the number of whorls on the left hand (J = 0.5). The correlation analysis between the dermatoglyphic indicators and the type of IAH inactivation showed that there are reliable connections between them (p < 0.05), but their number differs significantly in groups. In patients with ineffective chemoprophylaxis, the number of correlations (n = 13) exceeded that of the alternative group (n = 2) by more than 6 times, which indicates significant structural phenotypic differences. Conclusions. There were significant correlations between the type of IAH inactivation and dermatoglyphic indicators, but the number of such connections was 6 times higher in children with ineffective chemoprophylaxis than in the alternative group. This indicates that a more pronounced integration of dermatoglyphic genes and the ability to neutralize IAH is a favorable moment in general, but negative in relation to the effectiveness of tuberculosis prevention.

Synthesis and biological evaluation of some novel benzoxazin-4-one and quinazolin-4-one derivatives based on anti-inflammatory commercial drugs

Benzoxazine and quinazoline are nitrogen-containing heterocyclic scaffolds found in various biologically active compounds. Due to their diverse biological actions, these heterocyclic rings serve as crucial frameworks for designing medicinal compounds. This study aimed to synthesize and assess in vivo anti-inflammatory, analgesic, and low ulcerogenic potential of a few novel benz[d][1,3]-oxazin-4-one and quinazolinone derivatives. Benzoxazinones (3a-e) were synthesized by cyclizing the carboxylic group (-COOH) of five nonsteroidal anti-inflammatory drugs viz., aceclofenac, ibuprofen, diclofenac, mefenamic acid and ketoprofen (2a-e) with anthranilic acid (1) using dry phosphorus oxychloride (POCl3) in pyridine. The corresponding quinazolinone derivatives (5a-e) were obtained by reacting 3a-e with isonicotinic acid hydrazide (4). Both sets of compounds were evaluated for their anti-inflammatory, analgesic effects, and ulcerogenicity in animal models. Structural characterization was performed using spectral analysis. Among the benzoxazinone derivatives, compound 2-(2-((2,6-dichlorophenyl) amino) benzyl)-4H-benzo[d][1,3]oxazin-4-one (3d) exhibited significant anti-inflammatory activity (62.61% inhibition of rat paw edema) and analgesic activity (62.36% protection in acetic acid-induced writhings) with tolerable gastrointestinal toxicity (2.67 ulcerogenicity index) compared to quinazolinone derivatives. The results of anti-inflammatory and analgesic activities of both the series are comparable with the respective, positive control. Compound 3d, a benzoxazinone-diclofenac hybrid, emerged as a lead molecule with potent anti-inflammatory, analgesic activities and moderate gastric toxicity showcasing the promising potential for further development.

Новые полимерные комплексы гидразида изоникотиновой кислоты противотуберкулезного и иммуностимулирующего действия

Туберкулез относится к одному из социально значимых заболеваний. В научной литературе обосно-вана целесообразность использования полимерных матриц для иммобилизации протуберкулезных препаратов, что способствует завершению фагоцитоза. Проведено сравнительное исследование противотуберкулезной активности аналогов конденсата гидразида изоникотиновой кислоты при лечении экспериментального туберкулеза у мышей. Установлена эффективность использования хлоргидроксихитозанового комплекса с 1-изоникотинил-2-D-глюкозилгидрозон с включенным Со2+ в сравнении с хитозан-кобальт-1-изоникотинил-2-D-глюкозилгидрозоном при лечении экспериментального туберкулеза. Выявлена иммуностимулирующая активность полимерного металлокомплекса, сравнимая с комплексом хитозан-кобальт-1-изоникотинил-2-D-глюкозилгидрозон. Полученные в эксперименте ре-зультаты могут использоваться при разработке современных методов лечения туберкулеза.

Methylene blue-assisted molecularly-imprinted film modified nitrogen and sulfur co-doped molybdenum carbide for simultaneous electrochemical determination of two hepatotoxic drugs.

A novel electrochemical sensor with a dual-template molecular imprinting technology was fabricated for the simultaneous detection of paracetamol (PAR) and isoniazid (INZ). The sensor was constructed using nitrogen and sulfur co-doped molybdenum carbide (N, S@Mo2C) and a thin layer of electro-polymerized methylene blue was applied onto the surface of the N, S@Mo2C. The electrochemical sensor demonstrated remarkable analytical efficiency for the concurrent PAR and INZ quantification under optimal circumstances. The system achieved an exceptionally low limit of detection (S/N = 3) of 3.7 nM for PAR, with a concentration range of 0.013 and 140 µM. ALOD of7.6 nM was attained for INZ, with a linear range between 0.025 and 140 µM. Furthermore, the platform's selectivity was evaluated using differential pulse voltammetry (DPV). The designed platform successfully detected PAR and INZ in authentic samples with recoveries varying between 98.3% and 104.9%. The relative standard deviations (RSD) for these measurements ranged from 2.7 to 4.0%, demonstrating that the proposed sensor is extremely stable, repeatable, and reproducible. These promising results suggest that the sensor holds potential for the detection of various (bio) molecules, paving the way for future applications in sensing fields.

Preparative and Catalytic Properties of MoVI Mononuclear and Metallosupramolecular Coordination Assemblies Bearing Hydrazonato Ligands.

A series of polynuclear, dinuclear, and mononuclear Mo(VI) complexes were synthesized with the hydrazonato ligands derived from 5-methoxysalicylaldehyde and the corresponding hydrazides (isonicotinic hydrazide (H2L1), nicotinic hydrazide (H2L2), 2-aminobenzhydrazide (H2L3), or 4-aminobenzhydrazide (H2L4)). The metallosupramolecular compounds obtained from non-coordinating solvents, [MoO2(L1,2)]n (1 and 2) and [MoO2(L3,4)]2 (3 and 4), formed infinite structures and metallacycles, respectively. By blocking two coordination sites with cis-dioxo ligands, the molybdenum centers have three coordination sites occupied by the ONO donor atoms from the rigid hydrazone ligands and one by the N atom of pyridyl or amine-functionalized ligand subcomponents from the neighboring Mo building units. The reaction in methanol afforded the mononuclear analogs [MoO2(L1-4)(MeOH)] (1a-4a) with additional monodentate MeOH ligands. All isolated complexes were tested as catalysts for cyclooctene epoxidation using tert-butyl hydroperoxide (TBHP) as an oxidant in water. The impact of the structure and ligand lability on the catalytic efficiency in homogeneous cyclooctene epoxidation was elucidated based on theoretical considerations. Thus, dinuclear assemblies exhibited better catalytic activity than mononuclear or polynuclear complexes.

Ionic Liquid-Based Polymer Matrices for Single and Dual Drug Delivery: Impact of Structural Topology on Characteristics and In Vitro Delivery Efficiency.

Previously reported amphiphilic linear and graft copolymers, derived from the ionic liquid [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA_Cl‾), along with their conjugates obtained through modification either before or after polymerization with p-aminosalicylate anions (TMAMA_PAS‾), were employed as matrices in drug delivery systems (DDSs). Based on the counterion type in TMAMA units, they were categorized into single drug systems, manifesting as ionic polymers with chloride counterions and loaded isoniazid (ISO), and dual drug systems, featuring ISO loaded in self-assembled PAS conjugates. The amphiphilic nature of these copolymers was substantiated through the determination of the critical micelle concentration (CMC), revealing an increase in values post-ion exchange (from 0.011-0.063 mg/mL to 0.027-0.181 mg/mL). The self-assembling properties were favorable for ISO encapsulation, with drug loading content (DLC) ranging between 15 and 85% in both single and dual systems. In vitro studies indicated ISO release percentages between 16 and 61% and PAS release percentages between 20 and 98%. Basic cytotoxicity assessments using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) test affirmed the non-toxicity of the studied systems toward human non-tumorigenic lung epithelial cell line (BEAS-2B) cell lines, particularly in the case of dual systems bearing both ISO and PAS simultaneously. These results confirmed the effectiveness of polymeric carriers in drug delivery, demonstrating their potential for co-delivery in combination therapy.

A New Azomethine Chemosensor for Naked-Eye Detection of CN− and AcOˉ: Application to Determination of Cyanide in Some Agro-Products and Poisoned Human Blood Samples

A new symmetrical azomethine probe, H2L, has been synthesized via a condensation reaction of N, N´-Ethylene bis (3-formyl-5-methyl salicylaldimine), with Isonicotinic hydrazide in EtOH. The anion recognition studies exhibited that H2L acts as a chemosensor for the detection of CN− and AcO− in pure DMSO and DMSO/H2O 90:10(V/V) media over other basic anions such as F−, Cl−, Br−, I−, N3 −, SO4 2−, SO3 2−, PO4 3−, H2PO4 −, HSO4 −, NO2 −, and NO3 −. The ability of the H2L for rapid colorimetric sensing of CN− and AcOˉ was studied using UV–Vis, and 1H NMR titration methods. The detection limits of H2L toward CN− and AcO− in the semi-aqueous medium were found to be 2.12 and 2.63 μM, respectively, which are lower than the LOD of some existing azomethine probes. Effectively, H2L was used to qualitatively and quantitatively detect cyanide ions in the human-poisoned blood and some of the agro-products containing cyanogenic samples without relying on expensive instruments.

Drug resistance and the genotypic characteristics of rpoB and katG in rifampicin- and/or isoniazid-resistant Mycobacterium tuberculosis isolates in central Vietnam.

Tuberculosis (TB) and drug-resistant TB (DR-TB) are national health burdens in Vietnam. In this study, we investigated the prevalence of rifampicin (RIF) and/or isoniazid (isonicotinic acid hydrazide, INH) resistance in patients with suspected TB, and applied appropriate techniques to help rapidly target DR-TB. In total, 1,547 clinical specimens were collected and cultured using the BACTEC MGIT system (Becton Dickinson and Co.). A resazurin microtiter assay (REMA) was used to determine the proportions of RIF and/or INH resistance. A real-time polymerase chain reaction panel with TaqMan probes was employed to identify the mutations of rpoB and katG associated with DR-TB in clinical isolates. Genotyping of the identified mutations was also performed. A total of 468 Mycobacterium tuberculosis isolates were identified using the REMA. Of these isolates, 106 (22.6%) were found to be resistant to 1 or both antibiotics. Of the resistant isolates, 74 isolates (69.8%) were resistant to isoniazid (INH) only, while 1 isolate (0.94%) was resistant to RIF only. Notably, 31 isolates (29.24%) were resistant to both antibiotics. Of the 41 phenotypically INH-resistant isolates, 19 (46.3%) had the Ser315Thr mutation. There were 8 different rpoB mutations in 22 (68.8%) of the RIF-resistant isolates. The most frequently detected mutations were at codons 531 (37.5%), 526 (18.8%), and 516 (6.3%). To help prevent new cases of DR-TB in Vietnam, it is crucial to gain a comprehensive understanding of the genotypic DR-TB isolates.

Numerous Heterocyclic Compounds with an Isonicotinic Moiety have Been Studied for Their Synthesis, Antibacterial, Anticancer, Docking Simulation, and DFT Characteristics

In this elucidation, we focused on the synthesis of isonicotinic heterocyclic molecules through reaction of isonicotinic acid hydrazide with phthalic anhydride, which produced an excellent yield of the equivalent N-(1,3-dioxoisoindolin-2-yl)isonicotinamide (3), and isonicotinic acid hydrazide can react easily with different aldehydes to form derivatives of Schiff bases. Furthermore, the reactivity of hydrazide with CS2 which cyclized in the presence of acid to give the corresponding 1,3,4-oxadiazole in derivative 7, and the presence of NH2NH2 produced a 1H-1,2,4-triazole derivative 9 that readily reacted with phenacyl bromide with the elimination of -HBr to produce 6-phenyl-3-(pyridine-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (11). Hydrazide 1 reacts readily with many methylene compounds to produce a wide range of heterocycles. The presence of each produced heterocyclic was confirmed by spectral analysis investigation. Moreover, the synthesized compounds exhibited antimicrobial and antitumor activity against HepG2 liver tumor cells and neck squamous cell carcinoma (HNSCC) cancer cells, and the result was confirmed with different proteins through molecular docking simulation. Moreover, the optimization of the nicotinic compounds with DFT/B3LYP-631(G) basis set and determination of their physical descriptors correlated for its biological evaluation.

Mixed Ligand Complexes of Ni2+, Cu2+ and Zn2+ Ions Containing N-(4-methoxybenzylidene)isonicotinohydrazone Schiff Base and 1,10-Phenanthroline : Synthesis, Characterization, Antimicrobial and Antioxidant Properties

N-(4-methoxybenzylidene) isonicotinohydrazone (L1) Schiff base ligand was prepared by the condensation reaction of isonicotinic acid hydrazide (INH) and 4-methoxybenzaldehyde. A series of metal complexes of Ni2+, Cu2+ and Zn2+ ions was synthesized with Schiff base ligand (primary ligand, L1) and 1, 10-phenanthroline (L2) as a secondary ligand in stoichiometry ratio (1:1:1). Moreover, the synthesized ligand and its complexes have been characterized by analytical and physical properties, conductivity, magnetic susceptibility measurements, FTIR-spectra, and UV-Visible spectra. Conductivity measurements indicated that all complexes were 1:2 electrolytic in nature. IR spectra recommended that the oxygen of the carbonyl group (=CO) and nitrogen of the azomethine group (-C=N) were coordinated with metal ions. The confirmation of a square planar structure for Ni2+ and Cu2+ complexes, as well as a tetrahedral structure for the Zn2+ ion complex, was supported by their respective magnetic moment values and UV-Visible spectra. The antimicrobial activity of the metal complexes formed by L1 and L2 was evaluated against Escherichia coli and Pseudomonas sp. The metal complexes formed by the combination of L1 and L2 were subjected to testing against Escherichia coli and Pseudomonas sp. The Zn(II) complex exhibited superior antibacterial activity compared to the reference drug Kanamycin-30 against both bacterial strains in the tested compounds. In addition, the synthesised metal complexes demonstrated a comparatively moderate level of antioxidant activity when compared to the Schiff base. The Cu2+-complex exhibited the highest level of activity, while the Zn2+ -complex demonstrated the lowest antioxidant activity, which was comparable to that of BHT.

Microwave-assisted rapid catalytic degradation of isoniazid drug using polythiophene/ZnFe2O4 organic-inorganic hybrids

This present work reports for the first time, microwave-assisted catalytic degradation of isoniazid drug using organic–inorganic hybrids of polythiophene (PTh) decorated ZnFe2O4 nanoparticles. The hybrids were characterized using fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscopy along with energy dispersive spectra (SEM-EDS). The nanohybrids were used as catalysts for the degradation of isoniazid (ISN) drug under microwave irradiation. Almost 94% degradation of isoniazid was attained within 24 min using 100 mg of the catalyst. The degraded drug fragments were analyzed using LCMS and a tentative mechanism of degradation was proposed.

Supramolecular phenolic network-engineered C–CeO2 nanofibers for simultaneous determination of isoniazid and hydrazine in biological fluids

Electrochemical sensing provides a powerful technological means for the therapeutic drug monitoring of drug-resistant tuberculosis but requires a functionalized electrode to capture the analytes and catalyze their redox reactions. Herein, we construct a nickel–tannic acid supramolecular network (Ni–TA) on the surface of electrospun-derived C–CeO2 nanofiber for the sensitive and simultaneous detection of isoniazid (INZ) and hydrazine (HYD). Mechanistic investigations demonstrate that Ni–TA is electronegative and hydrophilic, thus facilitating an efficient mass and electron transfer. Ni–TA/C–CeO2 has higher adsorption rate constants (0.091 g mg–1 h–1 for INZ, and 0.062 g mg–1 h–1 for HYD) than native C–CeO2 (0.075 g mg–1 h–1 for INZ, and 0.047 g mg–1 h–1 for HYD). Moreover, Ni–TA/C–CeO2 (56 Ω) has lower charge transfer resistances than C–CeO2 (417 Ω). Ni–TA/C–CeO2 performs low detection limits and wide linearity ranges for INZ (0.012 µmol/L and 0.1–400 µmol/L, respectively) and HYD (0.008 µmol/L and 0.015–1420 µmol/L, respectively), coupled with high selectivity, cycle stability and reproducibility. This research demonstrated the promising applications of Ni–TA/C–CeO2 by analyzing human-collected plasma and urine samples.

Reaction of <i>o</i>-formylbenzoic acid with hydrazides of (iso)niconitic and hydroxybenzoic acids

The reaction of nicotinic and isonicotinic acid hydrazides with o -formyl benzoic acid in ethanol led to the formation of the corresponding hydrazones. It was found that o -formyl benzoic acid reacted in aldehyde form with hydrazides to form hydrazones. When heated in acetic anhydride, the latter are smoothly cyclized into 3-acetoxyisoindoline-1-ones. Structure of the synthesized compounds was proved by 1H and 13C NMR spectroscopy data. Antiradical and antiviral activity of the synthesized hydrazones and 3-acetoxyisoindoline-1-ones was studied. A compound with a wide spectrum of virus-inhibiting action against strains of the A virus was identified.

The impact of self-administered vaginal isonicotinic acid hydrazide (INH) administration 12 hours prior to levonorgestrel-releasing intrauterine system in women delivered only by elective cesarean section: A randomized double blinded clinical trial

The impact of self-administered vaginal isonicotinic acid hydrazide (INH) administration 12 hours prior to levonorgestrel-releasing intrauterine system in women delivered only by elective cesarean section: A randomized double blinded clinical trial

Synthesis, X-ray Structure, Hirshfeld, DFT Conformational, Cytotoxic, and Anti-Toxoplasma Studies of New Indole-Hydrazone Derivatives.

The hydrazones 3a-c, were synthesized from the reaction of indole-3-carbaldehyde and nicotinic acid hydrazide, isonicotinic acid hydrazide, and benzoic acid hydrazide, respectively. Their structures were confirmed using FTIR, 1HNMR, and 13CNMR spectroscopic techniques. Exclusively, hydrazones 3b and 3c were confirmed using single crystal X-ray crystallography to exist in the Eanti form. With the aid of DFT calculations, the most stable configuration of the hydrazones 3a-c in gas phase and in nonpolar solvents (CCl4 and cyclohexane) is the ESyn form. Interestingly, the DFT calculations indicated the extrastability of the EAnti in polar aprotic (DMSO) and polar protic (ethanol) solvents. Hirshfeld topology analysis revealed the importance of the N…H, O…H, H…C, and π…π intermolecular interactions in the molecular packing of the studied systems. Distribution of the atomic charges for the hydrazones 3a-c was presented. The hydrazones 3a-c showed a polar character where 3b has the highest polarity of 5.7234 Debye compared to the 3a (4.0533 Debye) and 3c (5.3099 Debye). Regarding the anti-toxoplasma activity, all the detected results verified that 3c had a powerful activity against chronic toxoplasma infection. Compound 3c showed a considerable significant reduction percent of cyst burden in brain homogenates of toxoplasma infected mice representing 49%.