Innovative Hybrid Compounds Targeting Tuberculosis: Development, Characterization and Bioefficacy analysis of 6-substituted-2-Chloroquinoline-3-Carbaldehyde Hydrazide Ester derivatives

This study delves into the biological activity of ester compounds obtained from analogues of 6-substituted-2-chloroquinoline-3-carbaldehyde hydrazide, aiming to exploit the combined antitubercular properties of quinoline and hydrazide to create innovative hybrid compounds. The molecules underwent a meticulous multi-step synthesis process, followed by purification through recrystallization. Methodologies such as 1H NMR, 13C NMR, FTIR and Mass Spectrometry was used to confirm the molecular structures of developed derivatives. SWISSADME, an online tool, was utilized to predict the ADME properties, shedding light on their pharmacokinetic profiles. Evaluation of in vitro antitubercular activity employing the Alamar blue method highlighted compounds 4a and 4f, exhibiting noteworthy efficacy achieving threshold concentrations of 6.25 µg/ml for M. tuberculosis inhibition. These findings suggest the possibility of novel quinoline Scaffold as potential molecule for TB treatment, contributing to ongoing endeavors in TB drug discovery and potentially laying the groundwork to develop effective antitubercular therapies.

Content Determination of Potential Genotoxic Impurity Maleic Hydrazide in Azintamide / 中国药房

OBJECTIVE：To establish a method for the content determination of potential genotoxic impurity maleic hydrazide in azintamide raw material. METHODS ：HPLC-FLD method was adopted. The determination was performed on Thermo Syncronis C18 column with mobile phase consisted of 0.2 mol/L acetic acid-methanol （gradient elution ）. The column temperature was set at 30 ℃，the excitation wavelength was 315 nm and emission wavelength was 389 nm. The flow rate was 1 mL/min，and the sample size was 20 μL. RESULTS：The blank solvent and azintamide did not interfere with the determination of maleic hydrazide. The linear range of maleic hydrazide was 19.5-300 ng/mL（r＝0.999 9）. The limit of detection was 4.5 ng/mL and the limit of quantification was 19.5 ng/mL. The recovery ranged from 98.79％ to 103.76％（RSDs were lower than 3.00％，n＝9）. RSDs of precision and stability （24 h）tests were no more than 5.63％，and those of durability tests were less than 2.00％（n＝6）. Maleic hydrazide was not detected in 3 batches of azinamide raw material. CONCLUSIONS ：The method is specific ，sensitive and accurate. It can be used for the trace determination of maleic hydrazide in azintamide or other matrix.

Hydrazide chemistry based enrichment method for N-glycoprotein analysis from human plasma exosomes / 中国药理学与毒理学杂志

OBJECTIVE To analyze the composition and function of N-glycoproteins in human plasma exosomes. METHODS Exosomes from human plasma were extracted by ultracentrifugation. The proteins from plasma exosomes were released by ultrasound and the obtained proteins were enzymatically degraded by trypsin to peptides. The N-glycopeptides in the mixture of the digested peptides was enriched by the hydrazide resin. The enriched N-glycoproteins were identified by mass spectrometry and subjected to gene ontology (GO) annotation analysis. RESULTS The plasma exosomes isolated by ultracentrifugation had a typical cup-shaped structure and the particle sizes were approximately 100 nm. Totally, 252 N-glycosylation sites corresponding to 131 N-glycoproteins were enriched and identified from exosomes of 1 mL human plasma digestion, which participated in many important biological processes, such as serine-type endopeptidase activity, serine-type endopeptidedase inhibitor acitivity and calcium ion binding. Sixty-seven of the N-glycoproteins had close relations with the occurrence of diseases. CONCLUSION Totally, 131 N-glycoproteins were identified in the research from the plasma exosome protein. These N-glycoproteins precipitate in many important biological processes and have close correlations with the occurrence and progression of various diseases.

Hirshfeld Surface and Structure Analysis of Two Co-crystal of Isonicotinic Acid Hydrazide / 医药导报

Objective Two co-crystals of isonicotinic acid hydrazide(INH)-malonic acid and INH-glutaric acid were prepared.The formation mechanism and intermolecular interaction were studied. Methods Three-dimensional structure of 2 co-crystals were obtained though single crystal X-ray diffraction(SXRD), and intermolecular interaction was analyzed using Hirshfeld surface method. Results INH-malonic acid crystalized in stoichiometric ratio of 1:0.5,while INH-glutaric acid in 1:1.Two co-crystals maintain their stable arrangement in space by hydrogen bond and van der Waals force. Conclusion With the existence of pyridine ring and carbohydrazide group in INH,which mainter-molecular interaction in co-crystal can be directly and clearly revealed by Hirshfeld surface analysis.

Synthesis, antimicrobial evaluation and QSAR studies of N'-benzylidene/(1-phenylethylidene)undec-10-enehydrazides.

A series of N'-benzylidene/(1-phenylethylidene)undec-10-enehydrazide was synthesized starting from undec-2-enoic acid through multi-step reactions. Synthesized derivatives were evaluated for their in vitro antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Aspergillus niger and Candida albicans by tube dilution method. The preliminary results showed the significance of o-NO2, m-NO2 and m-OCH3 groups at phenyl ring in describing antimicrobial activity of synthesized compounds. QSAR studies revealed that second order molecular connectivity index (2χ) and Balaban topological index (J) are the key parameters for antimicrobial activity of synthesized hydrazide derivatives and can be cosidered as important factors for interaction with target site of different microorganisms. It is pertinent to note that multi-target QSAR models were more significant in demonstrating the antimicrobial activity than one-target QSAR models.

A Case of Anagen Effluvium Induced by INH (Isonicotinic Acid Hydrazide) / 대한피부과학회지

We report a case of a 30 year-old woman who presented with acute scalp hair loss induced by isonicotinic acid hydrazide gap (INH). Considerable hair loss started within 4 weeks of INH administration. There was no evidence of dermatitis, allergic reaction, or any other cause for the hair loss. INH was discontinued, and the hair loss stopped within 4 weeks, with new hair growth seen. There was complete recovery of hair loss after 12 weeks of alopecia. Medication-induced hair loss is an occasional adverse effect of many drugs, however hair loss induced by INH has been reported in only 1 case. The complete recovery from anagen effluvium is difficult to explain, but it could have been due to the early discontinuance of INH.

Oscillopolarographic Determination of Maleic Hydrazide / 昆明医科大学学报

In the supporting electrolyte of 0.2mol/L LiCl, a distinct cathodic wave was produced by using first or seeondary derivative oscillopolarography to measure maleic hydrazide.The peak potential was -1.95V (Vs.SCE).The peak current was linearly proportional to the concentration of maleic hydrazide in the range of 1.0?10~(-4)mol/L to 2.0?10~(-5)mol/L and 1.5?10~(-5)mol/L to 4.0?10~(-6)mol/L.(PH5.6～9.3).The detection limit was lower than 2.0 ?10~(-6)mol/L.The error of various methods(relative deviation)was less than 0.3 per cent. Therefore,a simple,rapid and accurate analytical method for determining the purity of maleic hydrazide has been afforded in this paper.

N-[2-Naphthyl]-glycine hydrazide, a potent inhibitor of DNAdependent RNA polymerase of Mycobacterium tuberculosis H37Rv.

N-[2-Naphthyl]-glycine hydrazide has been shown for the first time as a potent inhibitor of the DNA-dependent RNA polymerase (EC 2.7.7.6) of Mycobacterium tuberculosis H37Rv. At a concentration of 10–9 M, the compound shows maximum inhibition of the enzyme, the inhibition being less at higher concentrations. It is suggested that the novel type of inhibition pattern may be due to hydrophobic interactions occurring between the molecules of the compound at higher concentrations. The finding that there is a shift in the λmax of the compound could also account for this phenomenon. The effect of this compound was also tested on DNA-dependent RNA polymerases from an eukaryotic fungus, Microsporum canis. At a concentration of 10–9 Μ it inhibits RNA polymerase II (32%) but not RNA polymerases I and III.

Effect of cupric-isonicotinic acid hydrazide complex on avian myeloblastosis virus reverse transcriptase and its associated enzyme activities.

Cupric complex of isonicotinic acid hydrazide inhibits DNA synthesis by avian myloblastosis virus reverse transcriptase. This inhibition occurs in the presence of either ribonucleotide or deoxyribonucleotide templates. The inhibition of reverse transcriptase by cupric-INH complex is considerably reduced when stored or proteolytically cleaved enzyme was used in the reaction. The complex also inhibits the reverse transciptase-associated RNase Η activity. The cupric-isonicotinic acid hydrazide complex cleaves pBR 322 from I DNA into smaller molecules in the presence or absence of reverse transcriptase-associated endonuclease. However, in the presence of the enzyme the DNA is cleaved to a greater extent.

Evaluation of mutagenicity of the antitubercular naphthylglycine hydrazides in Salmonella typhimurium.

N-(2-naphthyl)glycine hydrazide and N-methyl-N-(2-naphthyl) glycine hydrazide, which inhibit Mycobacterium tuberculosis H37 RV and show activity against experimental tuberculosis, were evaluated for their mutagenic potential in Salmonella typhimurium. Both the compounds at concentration ranges from 0·1 μg/plate to 1000 μg/plate failed to induce mutations at the histidine locus either directly or after treatment with rat liver homogenate fraction- "S-9". N-(2-naphthyl)glycine hydrazide and its N-methyl derivative elicited toxicity at concentrations of 500 μg/plate and 1000 μg/plate. However, in the presence of the liver homogenate system, reduction in toxicity was noticed probably due to detoxification and/ or conjugation of the compounds. Under the assay conditions employed, standard mutagens like 4-nitroquinoline-N-oxide, 9-aminoacridine and benzo(a)pyrene were positive. The nonmutagenic nature of N-(2-naphthyl)glycine hydrazide and N-methyl-N-(2-naphthyl)glycine hydrazide should enhance their potential for inclusion in treatment protocols for management of tuberculosis.

Effect of cupric-isonicotinic acid hydrazide complex on normal and avian myeloblastosis virus-infected cells cultivated in vitro.

The cupric complex of isonicotinic acid hydrazide was found to be nontoxic to normal yolk sac macrophages upto a concentration of 100 μΜ. At this concentration the complex did not significantly inhibit DNA, RNA or protein synthesis in these cells. The complex inhibited the avian myeloblastosis virus multiplication in these cells when added 0–4 h post-infection as demonstrated by the inhibition of both focus formation and expression of viral specific antigens. This inhibition was not observed when the complex was added 8 and 16 h after avian myeloblastosis virus infection. The studies carried out on avian myeloblastosis virus-transformed myeloblasts indicated that the complex had no effect on the colony (focus) formation. The results suggest that the complex inhibits the virus multiplication by interfering in an early event of viral growth cycle, possibly the process of reverse transcription.