Enamines as novel antibacterials and their structure-activity relationships.
Twenty-six enamines were synthesized to screen for the antimicrobial activity. Out of the compounds, 22 were reported for the first time. Their chemical structures including E/Z-configurations were clearly determined by 1H NMR, ESI mass spectra and elemental analyses, coupled with three selected single-crystal structures. In general, these synthetic compounds were shown to be more effective to inhibit growth of bacteria than fungi. The most active compound, (E)-ethyl 3-(4-hydroxyphenylamino)-2-(4-chlorophenyl)acrylate (1b), showed considerable antibacterial activities against Staphylococcus aureus ATCC 6538 with MIC of 0.5 microg/mL and against Pseudomonas fluorescens ATCC 13525 with MIC of 1.5 microg/mL, which was superior to the positive controls penicillin and kanamycin, respectively. Structure-activity relationship analysis revealed: as for A-ring, the compounds substituted at 3,5-positions were more active than 2,4-position-substituted derivatives, and halo-substituted analogs at 2-position had essentially same activities as the 4-position-substituted derivatives. Increase of steric hindrance around the nitrogen atom led to an inactive compound.
Xiao
Zhu-Ping
ZP
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Fang
Rui-Qin
RQ
Li
Huan-Qiu
HQ
Xue
Jia-Yu
JY
Zheng
Yi
Y
Zhu
Hai-Liang
HL
D000588:Amines / Q000737:chemistry* / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000588:Amines; D000890:Anti-Infective Agents