Synthesis and biological evolution of hydrazones derived from 4-(trifluoromethyl)benzohydrazide

Martin Krátký, Sz. Bősze, Zsuzsa Baranyai, Jiřina Stolaříková, Jarmila Vinšová

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Reflecting the known biological activity of isoniazid-based hydrazones, seventeen hydrazones of 4-(trifluoromethyl)benzohydrazide as their bioisosters were synthesized from various benzaldehydes and aliphatic ketones. The compounds were screened for their in vitro activity against Mycobacterium tuberculosis, nontuberculous mycobacteria (M. avium, M. kansasii), bacterial and fungal strains. The most antimicrobial potent derivatives were also investigated for their cytostatic and cytotoxic properties against three cell lines. Camphor-based molecule, 4-(trifluoromethyl)-N′-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)benzohydrazide, exhibited the highest and selective inhibition of M. tuberculosis with the minimum inhibitory concentration (MIC) of 4 µM, while N′-(4-chlorobenzylidene)-4-(trifluoromethyl)benzohydrazide was found to be superior against M. kansasii (MIC = 16 µM). N′-(5-Chloro-2-hydroxybenzylidene)-4-(trifluoromethyl)benzohydrazide showed the lowest MIC values for gram-positive bacteria including methicillin-resistant Staphylococcus aureus as well as against two fungal strains of Candida glabrata and Trichophyton mentagrophytes within the range of ≤0.49–3.9 µM. The convenient substitution of benzylidene moiety at the position 4 or the presence of 5-chloro-2-hydroxybenzylidene scaffold concomitantly with a sufficient lipophilicity are essential for the noticeable antimicrobial activity. This 5-chlorosalicylidene derivative avoided any cytotoxicity on two mammalian cell cultures (HepG2, BMMΦ) up to the concentration of 100 µM, but it affected the growth of MonoMac6 cells.

Original languageEnglish
Pages (from-to)5185-5189
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number23
DOIs
Publication statusPublished - Dec 1 2017

Keywords

  • 4-(Trifluoromethyl)benzohydrazide
  • Antibacterial activity
  • Antifungal activity
  • Cytostasis
  • Cytotoxicity
  • Hydrazone
  • Mycobacterium tuberculosis
  • Nontuberculous mycobacteria

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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