Synthesis, structure and structure–activity relationship analysis of caffeic acid amides as potential antimicrobials

A series of caffeic acid amides 1–23 were synthesized and nine of which (13–17, 19–21 and 23) were reported for the first time. The chemical structures of these compounds were confirmed by means of 1H NMR, ESI MS and elemental analyses. Compound 15 was determined by single-crystal X-ray diffraction analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT method. Compounds 10–12, 15, 18 and 21 showed considerable antibacterial activities against B. subtilis with MICs of 7.95, 6.25, 3.89, 1.18, 3.12 and 15.5 μg/mL, respectively. Structure–activity relationship analysis disclosed that caffeic acid anilides with electron-donating groups at p-position of benzene ring have better inhibitory activities.

Graphical abstractA series of caffeic acid amides were synthesized and (E)-3-(3,4-Dihydroxyphenyle)-N-p-tolylacrylamide (15) showed considerable antibacterial activity against Bacillus subtilis with MIC of 1.18 ug/mL.Figure optionsDownload full-size imageDownload as PowerPoint slide