Synthesis, biological evaluation and 3D-QSAR study of hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1-yl)quinoline as anti-tuberculosis agents

Eur J Med Chem. 2014 Oct 6:85:255-67. doi: 10.1016/j.ejmech.2014.07.100. Epub 2014 Jul 29.

Abstract

We report synthesis, anti-tuberculosis activity and 3D-QSAR study of forty nine hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1-yl)quinoline. The most potent compounds upon evaluation for anti-tuberculosis activity exhibited MIC99 of 3.125 μg/mL against Mycobacterium tuberculosis H37Rv strain. We applied the in silico technique of 3D-QSAR to study structure activity relationship of the synthesized compounds. The developed CoMFA model exhibited excellent r(2)ncv of 0.971, and r(2)cv of 0.543. The predicted r(2)pred of 0.883 showed that the predicted values were in good agreement with the experimental values. Further, the contour map analysis, suggested that the sterically bulky and electronegative substitutions at the para position of the phenyl ring are favorable for anti-tuberculosis activity.

Keywords: CoMFA; Hydrazide; Quinolines; Semicarbazide; Thiosemicarbazide; Tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemical synthesis
  • Adamantane / chemistry
  • Adamantane / pharmacology
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Hydrazines / chemistry*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Mycobacterium tuberculosis / drug effects
  • Quantitative Structure-Activity Relationship*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Semicarbazides / chemistry*

Substances

  • Antitubercular Agents
  • Hydrazines
  • Quinolines
  • Semicarbazides
  • thiosemicarbazide
  • Adamantane