Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis was written by Wen, Wuqiang;Cao, Hongxuan;Huang, Yunyuan;Tu, Jie;Wan, Chen;Wan, Jian;Han, Xinya;Chen, Han;Liu, Jiaqi;Rao, Li;Su, Chen;Peng, Chao;Sheng, Chunquan;Ren, Yanliang. And the article was included in Journal of Medicinal Chemistry in 2022.Related Products of 5388-42-1 This article mentions the following:
Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors of FBA from Candida albicans (CaFBA). Site-directed mutagenesis, liquid chromatog.-mass spectrometry, and the crystallog. structures of APO-CaFBA, CaFBA-G3P, and C157S-I revealed that S268 is an essential pharmacophore for the catalytic activity of CaFBA, and L288 is an allosteric regulation switch for CaFBA. Furthermore, most of the CaFBA covalent inhibitors exhibited good inhibitory activity against azole-resistant C. albicans, and compound II can inhibit the growth of azole-resistant strains 103 with the MIC80 of 1濠电偞鎸鹃幐?mL. Collectively, this work identifies a new covalent allosteric site of CaFBA and discovers the first generation of covalent inhibitors for fungal FBA with potent inhibitory activity against resistant fungi, establishing a structural foundation and providing a promising strategy for the design of potent antifungal drugs. In the experiment, the researchers used many compounds, for example, 2-Phenylisoindolin-1-one (cas: 5388-42-1Related Products of 5388-42-1).
2-Phenylisoindolin-1-one (cas: 5388-42-1) belongs to indole derivatives. Indole produced by Proteus, Pseudomonas, Escherichia and other species was shown to be a growth promoting factor in Arabidopsis thaliana. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Related Products of 5388-42-1
Referemce:
Indole alkaloid derivatives as building blocks of natural products from闂佽壈浜崹淇沜illus thuringiensis闂佽壈浜粋鍧闂佽壈浜崹淇沜illus velezensis闂佽壈浜粋鍧 their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles