New series of isoniazid hydrazones linked with electron-withdrawing substituents

Eva Vavříková, Slovenko Polanc, Marijan Kočevar, Janez Košmrlj, Kata Horváti, Szilvia Bsze, Jiřina Stolaříková, Aleš Imramovský, Jarmila Vinšová

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Abstract

A series of new isoniazid hydrazones was synthesized by two procedures. In the first isoniazid was activated with diethoxymethyl acetate and condensed with the appropriate anilines. Alternatively, substituted anilines were activated by diethoxymethyl acetate and subsequently condensed with isoniazid. NMR study confirmed that both synthetic approaches gave the same tautomer. All compounds were screened for in vitro antimycobacterial activity. Most of them exhibited the same activity against Mycobacterium tuberculosis (MIC 1 μmol L -1) as isoniazid (INH), better activity against Mycobacterium kansasii 325/80 (MIC 0.125-0.250 μmol L-1), high value of selectivity index (SI) and IC50 between 0.0218 and 0.326 mmol L -1. Compound 2o with the best SI was used as a model compound for the stability test and was found to be stable at neutral pH, but under acidic conditions it slowly hydrolysed.

Original languageEnglish
Pages (from-to)5902-5909
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number12
DOIs
Publication statusPublished - Dec 1 2011

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Keywords

  • Antitubercular drug
  • Hydrazone
  • In vitro activity
  • Isoniazid
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Vavříková, E., Polanc, S., Kočevar, M., Košmrlj, J., Horváti, K., Bsze, S., Stolaříková, J., Imramovský, A., & Vinšová, J. (2011). New series of isoniazid hydrazones linked with electron-withdrawing substituents. European Journal of Medicinal Chemistry, 46(12), 5902-5909. https://doi.org/10.1016/j.ejmech.2011.09.054