Discovery of Lipophilic Bisphosphonates That Target Bacterial Cell Wall and Quinone Biosynthesis was written by Malwal, Satish R.;Chen, Lu;Hicks, Hunter;Qu, Fiona;Liu, Weidong;Shillo, Alli;Law, Wen Xuan;Zhang, Jianan;Chandnani, Neal;Han, Xu;Zheng, Yingying;Chen, Chun-Chi;Guo, Rey-Ting;Abdel Khalek, Ahmed;Seleem, Mohamed N.;Oldfield, Eric. And the article was included in Journal of Medicinal Chemistry in 2019.Formula: C5H5NO This article mentions the following:
We report that alkyl-substituted bisphosphonates have activity against Bacillus anthracis Sterne (0.40娓璯/mL), Mycobacterium smegmatis (1.4娓璯/mL), Bacillus subtilis (1.0娓璯/mL), and Staphylococcus aureus (13娓璯/mL). In many cases, there is no effect of serum binding, as well as low activity against a human embryonic kidney cell line. Targeting of isoprenoid biosynthesis is involved with 74 having IC50 values of 閳?00 nM against heptaprenyl diphosphate synthase and 200 nM against farnesyl diphosphate synthase. B. subtilis growth inhibition was rescued by addition of farnesyl diphosphate, menaquinone-4 (MK-4), or undecaprenyl phosphate (UP), and the combination of MK-4 and UP resulted in a 25鑴?increase in ED50, indicating targeting of both quinone and cell wall biosynthesis. Clostridioides difficile was inhibited by I, and since this organism does not synthesize quinones, cell wall biosynthesis is the likely target. We also solved 3 X-ray structures of inhibitors bound to octaprenyl diphosphate and(or) undecaprenyl diphosphate synthases. In the experiment, the researchers used many compounds, for example, Pyridin-4-ol (cas: 626-64-2Formula: C5H5NO).
Pyridin-4-ol (cas: 626-64-2) belongs to pyridine derivatives. Pyridine has a conjugated system of six 锜?electrons that are delocalized over the ring. The molecule is planar and, thus, follows the H鐪塩kel criteria for aromatic systems. Pyridine derivatives are also useful as small-molecule 浼?helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Formula: C5H5NO