Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa.
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa.
Bioorg Med Chem. 2020 Jul 1;28(13):115530. doi: 10.1016/j.bmc.2020.115530. Epub 2020 Apr 25.
Fusidic acid (FA) is a potent congener of the fusidane triterpenoid class of antibiotics. Structure-activity relationship (SAR) studies suggest the chemical structure of FA is optimal for its antibacterial activity. SAR studies from our group within the context of a drug repositioning approach in tuberculosis (TB) suggest that, as with its antibacterial activity, the C-21 carboxylic acid group is indispensable for its anti-mycobacterial activity. Further studies have led to the identification of 16-deacetoxy-16β-ethoxyfusidic acid (58), an analog which exhibited comparable activity to FA with an in vitro MIC value of 0.8 µM. Preliminary SAR studies around the FA scaffold suggested that the hydrophobic side chain at C-20, like the C-11 OH group, was required for activity. The C-3 OH group, however, can be functionalized to obtain more potent compounds.
夫西地酸（FA）是一种强效的夫烷三萜类抗生素。构效关系（SAR）研究表明，FA 的化学结构是其抗菌活性的最佳选择。我们课题组在结核病（TB）药物再定位方法的背景下进行的 SAR 研究表明，与抗菌活性一样，C-21 羧酸基团对于其抗分枝杆菌活性是不可或缺的。进一步的研究导致了 16-去乙酰氧基-16β-乙氧基夫西地酸（58）的鉴定，该类似物的体外 MIC 值为 0.8µM，与 FA 的活性相当。围绕 FA 支架的初步 SAR 研究表明，C-20 上的疏水性侧链与 C-11 OH 基团一样，是活性所必需的。然而，C-3 OH 基团可以进行官能化以获得更有效的化合物。
