Synthesis and in vitro antimycobacterial and isocitrate lyase inhibition properties of novel 2-methoxy-2'-hydroxybenzanilides, their thioxo analogues and benzoxazoles

Eur J Med Chem. 2012 Oct:56:108-19. doi: 10.1016/j.ejmech.2012.08.016. Epub 2012 Aug 16.

Abstract

A new series of 2-methoxy-2'-hydroxybenzanilide derivatives and their thioxo analogues have been synthesised and characterised by IR, NMR and elemental analysis. These compounds were investigated for their in vitro antimycobacterial activities against Mycobacterium tuberculosis 331/88, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80, clinically isolated M. kansasii 6509/96 and the ability to act as in vitro isocitrate lyase inhibitors. The best ICL inhibitors were two compounds from the thiobenzanilide group (8f, 8m), which exhibited an inhibition potential that was equal to the standard compound, 3-nitropropionic acid. In addition, the best antimycobacterial properties were exhibited by benzanilide derivatives 6h, 6k and 6l with 5-Cl and 4' or 5' Cl/Br substitution. For all the thiobenzanilide derivatives tested, two conformers were observed in the NMR spectra, which is most likely due to the hindered rotation of the C-N bond.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / chemical synthesis
  • Anilides / chemistry
  • Anilides / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hep G2 Cells
  • Humans
  • Isocitrate Lyase / antagonists & inhibitors*
  • Isocitrate Lyase / metabolism
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium / drug effects*
  • Structure-Activity Relationship

Substances

  • 2-methoxy-2'-hydroxybenzanilide
  • Anilides
  • Antineoplastic Agents
  • Benzoxazoles
  • Enzyme Inhibitors
  • Isocitrate Lyase