克林沙星酰胺衍生物的简易合成及其体内外生物活性

Facile synthesis and in vitro/vivo bioactivities of amido derivatives of clinafloxacin

通过特色羧酸与克林沙星吡咯环氨基直接反应,得到19个未见文献报道的克林沙星酰胺衍生物,产物收率52.8%～97.5%.目标分子结构得到1HNMR,13CNMR,HRMS的确证.在琼脂扩散法初筛的基础上进行MIC活性验证,进而对活性较好的化合物开展急性毒性试验以及化合物稳定性实验,由此发现了抗菌活性更强、毒性更低、溶解性更大、稳定性更好的先导分子TM1-b和TM1-l,为该类分子的进一步研究奠定了基础.

Nineteen new amido derivatives of clinafloxacin （CF） were prepared in 52.8%～97.5% via the condensation of selected carboxylic acids with clinafloxacin. The chemical structures of these target molecules were confirmed by 1H NMR, 13C NMR and HR MS. Following the preliminary evaluation of antibacterial activity through agar diffusion method, the minimal inhibitory concentrations （MICs） of all the obtained amido derivatives of CF were measured by Micro-dilution method. The toxicity of the active compounds of interest was confirmed by acute toxicity test in mice. The stability of most of target compounds was detected by use of the general agar diffusion procedure on the keeping time of 30–90 days, subsequently. The results showed that TM1-b and TM1-l possessed stronger antibacterial activity, lower toxicity, larger solubility and higher stability than CF, and thus may be exploitable as lead compounds. This finding may provide some helpful guidances for further investigation.