1,2-二取代吡咯类化合物的体外抗衣原体活性研究

The antichlamydial activity of 1,2-disubstituted pyrrole derivatives in vitro

目的评估16个1,2-二取代吡咯类化合物的体外抗衣原体活性。方法通过测定化合物对沙眼衣原体L2、鼠衣原体MoPn和肺炎衣原体AR39感染性子代滴度的抑制效果,计算IC50值评估其抗衣原体活性。采用WST-1法测定细胞活力,评估化合物的细胞毒性作用。最后,借助EB预处理实验检测化合物对EB感染能力的影响,通过改变化合物处理时间评估其对衣原体增殖过程的影响。结果大部分化合物具有抗衣原体作用,其中化合物8的作用最强,其对三株衣原体的IC_(50)值在1.76-8.23μmol·L^(-1)之间。大部分化合物在16μmol·L^(-1)时具有明显的细胞毒性,8μmol·L^(-1)时细胞毒性明显降低。这些化合物主要通过干扰衣原体增殖的早中期来抑制衣原体的生长,同时也可以通过降低EB感染能力抑制衣原体的感染。结论1,2-二取代吡咯类化合物具有广谱抗衣原体活性,其抗衣原体作用与降低EB感染能力和干扰早中期RB增殖有关。

Aim To evaluate the antichlamydial activity of our previously synthesized sixteen 1,2-disubstituted pyrroles in vitro,providing candidate for the development of novel agents against Chlamydia.Methods Firstly,the inhibitory effect of compounds on the generation of infectious progeny EBs at different concentrations was analyzed for Chlamydia trachomatis L2(Ct L2),C.muridarum(Nigg II strain,known as MoPn)and C.pneumonia(Cpn AR39).The IC_(50) values were then calculated based on the percentage inhibition data,accounting for the antichlamydial activity of the compounds.Secondly,cell viability was determined by WST-1 to evaluate the toxic effects of the compounds on host cells.Finally,EB pretreatment assay was used to detect the influence of compounds on EB infectivity.Also,the impact of chemical exposure time on their antichlamydial effect was evaluated by later treatment and withdrawal assays.Results Most compounds inhibited at least one of the three tested Chlamydia strains.Among them,compound 8 exhibited the strongest inhibitory activity,with IC50 values from 1.76 to 8.23μmol·L^(-1) for three strains.Most of the compounds had toxic effect on host cells at 16μmol·L^(-1).The cytotoxicity was obviously dropped at 8μmol·L^(-1),when compound 8 showed no detectable cytotoxic effect.These pyrrole derivatives mainly disturbed the early-to-middle proliferation stage of chlamydial life cycle.Also,they partially inhibited Chlamydia infection by reducing EB infectivity.Conclusions 1,2-disubstituted pyrroles possess broad spectrum antichlamydial activity,related to reducing EB infectivity and interfering RB proliferation in the early and middle stages.