RESUMO
Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.
RESUMO
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.
RESUMO
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.
Assuntos
Adulto , Feminino , Humanos , Alopecia , Dermatite , Cabelo , Hipersensibilidade , Isoniazida , Couro CabeludoRESUMO
OBJECTIVE:To establish an HPLC method for content determination of isoniazid and isonicotinic acid in isoniazid tablets.METHODS:The determination was performed on SHIM-PACK VP-ODS C18 column.The mobile phase consisted of methanol-water(0.2% docusate sodium,40 :60) at a flow rate of 0.8 mL?min-1.The UV detection wavelength was set at 261 nm and the sample size was 5 ?L.RESULTS:The linear range was 10～1000 ?g?mL-1 for isoniazid(r=0.999 8) with average recovery of 99.57%(RSD=0.26%) and 2～24 ?g?mL-1 for isonicotinic acid(r=0.9994) with average recovery of 98.96%(RSD=0.96%).The limited quantities were 0.05 ?g?mL-1,0.16 ?g?mL-1,respectively.CONCLUSION:The established method is simple,rapid and accurate,and suitable for content determination of isoniazid tablets.
RESUMO
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.
RESUMO
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.
RESUMO
Metabolism of isonicotinic acid and isoniazid by Sarcina sp. led to the formation of two metabolites which were characterised as 2-hydroxyisonicotinic acid and citrazinic acid. The blue pigment formed during fermentation was shown to be derived from the auto-oxidation of citrazinic acid. 2-Oxo-glutarate accumulated as the major keto acid when isonicotinic acid or isonicotinic acid hydrazide metabolism was inhibited by 1 mM sodium arsenite. Isonicotinic acid, 2-hydroxyisonicotinic acid and 2-oxo-glutarate were oxidised by isonicotinic acid hydrazide or isonicotinic acid-grown cells; citrazinic acid was, however, not oxidised. Isoniazid hydrazine hydrolase, isonicotinic acid and 2-hydroxyisonicotinic acid hydroxylases were detected in the cell-free extract of Sarcina sp. grown on isonicotinic acid hydrazide or isonicotinic acid.