title: Enamines as novel antibacterials and their structure-activity relationships.
abstract: 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.
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Fang
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Xue
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: 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
chemical_list: D000588:Amines; D000890:Anti-Infective Agents