Xiao Zhu-Ping, Fang Rui-Qin, Li Huan-Qiu, Xue Jia-Yu, Zheng Yi, Zhu Hai-Liang
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Eur J Med Chem. 2008 Sep;43(9):1828-36. doi: 10.1016/j.ejmech.2007.11.026. Epub 2007 Dec 8.
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.
合成了26种烯胺以筛选其抗菌活性。在这些化合物中，有22种是首次报道。通过1H NMR、ESI质谱和元素分析，并结合三个选定的单晶结构，明确确定了它们的化学结构，包括E/Z构型。一般来说，这些合成化合物对细菌生长的抑制作用比真菌更有效。活性最高的化合物，(E)-3-(4-羟基苯氨基)-2-(4-氯苯基)丙烯酸乙酯(1b)，对金黄色葡萄球菌ATCC 6538显示出相当强的抗菌活性，MIC为0.5μg/mL，对荧光假单胞菌ATCC 13525的MIC为1.5μg/mL，分别优于阳性对照青霉素和卡那霉素。构效关系分析表明：对于A环，在3,5-位取代的化合物比在2,4-位取代的衍生物更具活性，2-位的卤代类似物与4-位取代的衍生物具有基本相同的活性。氮原子周围空间位阻的增加导致化合物无活性。
