Synthesis, structure, and structure-activity relationship analysis of enamines as potential antibacterials

Bioorg Med Chem. 2007 Jun 15;15(12):4212-9. doi: 10.1016/j.bmc.2007.03.060. Epub 2007 Mar 24.

Abstract

Twenty-four enamines were synthesized and reported for the first time. Their chemical structures were confirmed by means of 1H NMR, ESI mass spectra, and elemental analyses, and four of them were determined by single crystal X-ray diffraction analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Pseudomonas fluorescens ATCC 13525, and Staphylococcus aureus ATCC 6538) and antifungal (Aspergillus niger ATCC 16404, Candida albicans ATCC 10231, and Trichophyton rubrum ATCC 10218) activities by MTT method. Compounds (E)-ethyl 3-(4-hydroxyphenylamino)-2-(4-methoxyphenyl)acrylate (9b), (E)-ethyl 3-(3,5-difluorophenylamino)-2-(4-chlorophenyl)acrylate (11b), (E)-ethyl 3-(3,5-dichlorophenylamino)-2-(4-chlorophenyl)acrylate (12b), and (E)-ethyl 3-(4-methylphenylamino)-2-(4-chlorophenyl)acrylate (15b) showed considerable antibacterial activities against S. aureus ATCC 6538 with MICs of 3.8, 1.9, 1.1, and 0.9 microg/mL, respectively. Structure-activity relationship (SAR) analysis disclosed, generally, an E-isomer exhibited higher antibacterial activity than the corresponding Z-isomer. An electron-withdrawing group on A-ring led to some decrease in activity, while on B-ring, a similar substitution provided higher activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Spectrometry, Mass, Electrospray Ionization
  • Structure-Activity Relationship

Substances

  • Amines
  • Anti-Bacterial Agents