Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570, USA.
Bioorg Med Chem. 2009 Oct 15;17(20):7174-85. doi: 10.1016/j.bmc.2009.08.067. Epub 2009 Sep 6.
Methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Using high-throughput screening, we have identified several compounds that inhibit the enzymatic activity of the SrtA. A structure-activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC(50) values in the sub-micromolar range. Many of these molecules also inhibit the sortase enzyme from Bacillus anthracis suggesting that they may be generalized sortase inhibitors.
耐甲氧西林金黄色葡萄球菌（MRSA）是一个主要的健康问题，这就迫切需要新的抗生素。抑制金黄色葡萄球菌 SrtA 转肽酶的化合物可能具有强大的抗感染作用，因为这种酶将毒力因子附着在细胞壁上。我们使用高通量筛选技术，已经鉴定出几种能够抑制 SrtA 酶活性的化合物。构效关系（SAR）分析导致鉴定出几种哒嗪酮和吡唑硫酮类似物，它们以亚微摩尔范围内的 IC50 值抑制 SrtA。这些分子中的许多还抑制炭疽芽孢杆菌的转肽酶，这表明它们可能是通用的转肽酶抑制剂。
