黄嘌呤氧化酶抑制剂高通量筛选模型的建立及应用

 目的建立适用于高通量筛选的黄嘌呤氧化酶(xanthineoxidase,XO)抑制剂筛选模型,并以此模型进行XO抑制剂筛选。方法建立XO活性的紫外检测法及其抑制剂体外高通量筛选模型,并用此筛选模型对71760化合物与粗提物进行筛选。结果通过对筛选条件优化,建立了可靠的筛选模型,并对71760样品进行了初筛,发现27个活性化合物,命中率0.038%,其中17个有较好量-效关系。结论建立了稳定灵敏的适用于高通量筛选的XO抑制剂体外筛选模型,并发现了一些具有较好活性的化合物。

Establishment and Application of a High-Throughput Screening Assay for Xanthine Oxidase Inhibitor in Vitro

OBJECTIVE To establish a high-throughput assay for xanthine oxidase inhibitor screening.METHODS The activity of xanthine oxidase was assayed by ultraviolet spectrophotometry and the developed method was used to screen a set of 71 760 compounds in a high-throughput format. RESULTS The effective and reliable screening method was established.27 Compounds were identified from 71 760 compounds. The hits percent was 0.038% , among which 17 compounds were confirmed by subsequent test at multiple concentrations. The most potent compound showed an IC₅₀ of 93.7 nmol·L^-1. CONCLUSION The highly efficient and sensitive high-throughput screening method can be successfully used to identify xanthine oxidase inhibitor and some high active compounds were discovered.