21392-57-4Relevant articles and documents
Synthesis and evaluation of selenoflavones that have potential neuroprotective effects
Choi, Yong-Sung,Kim, Yoon-Jung,Lee, Ju Yeun,Lee, Jinu,Jeong, Jin-Hyun
, p. 2794 - 2805 (2014)
We synthesized selenoflavones and evaluated their physicochemical properties and antioxidant effects. When oxygen was substituted with selenium, the compounds exhibited improved polarity and lipophilicity, implying that this change could lead to better BBB penetration. Selenoflavones revealed more potent antioxidant activity in our in-vitro assay. This suggests that selenoflavones would be more druggable than flavones and have a better potential as a neuroprotective agent.
Discovery of human TyrRS inhibitors by structure-based virtual screening, structural optimization, and bioassays
Huang, Shenzhen,Wang, Xiang,Lin, Guifeng,Cheng, Jie,Chen, Xiuli,Sun, Weining,Xiang, Rong,Yu, Yamei,Li, Linli,Yang, Shengyong
, p. 9323 - 9330 (2019)
The human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS), which is well known for its essential aminoacylation function in protein synthesis, has been shown to translocate to the nucleus and protect against DNA damage caused by external stimuli. Small molecules that can fit into the active site pocket of TyrRS are thought to affect the nuclear role. The exploitation of TyrRS inhibitors has attracted attention recently. In this investigation, we adopted a structure-based virtual screening strategy and subsequent structure-activity relationship analysis to discover new TyrRS inhibitors, and identified a potent compound 5,7-dihydroxy-6,8-bis((3-hydroxyphenyl)thio)-2-phenyl-4H-chromen-4-one (compound 11, Ki = 8.8 μM). In intact HeLa cells, this compound showed a protective effect against DNA damage. Compound 11 is a good lead compound for the further development of drugs against disorders caused by DNA damage.
Biotransformation of 5,7-Methoxyflavones by Selected Entomopathogenic Filamentous Fungi
?u?ny, Mateusz,Tronina, Tomasz,Koz?owska, Ewa,Kostrzewa-Sus?ow, Edyta,Janeczko, Tomasz
, p. 3879 - 3886 (2021/05/04)
5,7-Dimethoxyflavone, a chrysin derivative, occurs in many plants and shows very low toxicity, even at high doses. On the basis of this phenomenon, we biotransformed a series of methoxy-derivatives of chrysin, apigenin, and tricetin obtained by chemical synthesis. We used entomopathogenic fungal strains with the confirmed ability of simultaneous hydroxylation/demethylation and glycosylation of flavonoid compounds. Both the amount and the place of attachment of the methoxy group influenced the biotransformation rate and the product's amount nascent. Based on product and semi-product structures, it can be concluded that they are the result of cascading transformations. Only in the case of 5,7,3′,4′,5′-pentamethoxyflavone, the strains were able to attach a sugar molecule in place of the methoxy substituent to give 3′-O-β-d-(4″-O-methylglucopyranosyl)-5,7,4′,5′-tetramethoxyflavone. However, we observed the tested strains' ability to selectively demethylate/hydroxylate the carbon C-3′ and C-4′ of ring B of the substrates used. The structures of four hydroxyl-derivatives were determined: 4′-hydroxy-5,7-dimethoxyflavone, 3′-hydroxy-5,7-dimethoxyflavone, 3′-hydroxy-5,7,4′,5′-tetramethoxyflavone, and 5,7-dimethoxy-3′,4′-dihydroxyflavone (5,7-dimethoxy-luteolin).
Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance
Brazier-Hicks, Melissa,Coxon, Christopher R.,Cummins, Ian,Edwards, Robert,Eno, Rebecca F. M.,Freitag-Pohl, Stefanie,Hughes, David J.,Mitchell, Glynn,Moore, Jenny,Onkokesung, Nawaporn,Pohl, Ehmke,Schwarz, Maria,Steel, Patrick G.,Straker, Hannah E.,Wortley, David J.
, p. 9211 - 9222 (2021/11/16)
The evolution and growth of multiple-herbicide resistance (MHR) in grass weeds continues to threaten global cereal production. While various processes can contribute to resistance, earlier work has identified the phi class glutathione-S-transferase (AmGSTF1) as a functional biomarker of MHR in black-grass (Alopecurus myosuroides). This study provides further insights into the role of AmGSTF1 in MHR using a combination of chemical and structural biology. Crystal structures of wild-type AmGSTF1, together with two specifically designed variants that allowed the co-crystal structure determination with glutathione and a glutathione adduct of the AmGSTF1 inhibitor 4-chloro-7-nitro-benzofurazan (NBD-Cl) were obtained. These studies demonstrated that the inhibitory activity of NBD-Cl was associated with the occlusion of the active site and the impediment of substrate binding. A search for other selective inhibitors of AmGSTF1, using ligand-fishing experiments, identified a number of flavonoids as potential ligands. Subsequent experiments using black-grass extracts discovered a specific flavonoid as a natural ligand of the recombinant enzyme. A series of related synthetic flavonoids was prepared and their binding to AmGSTF1 was investigated showing a high affinity for derivatives bearing a O-5-decyl-α-carboxylate. Molecular modelling based on high-resolution crystal structures allowed a binding pose to be defined which explained flavonoid binding specificity. Crucially, high binding affinity was linked to a reversal of the herbicide resistance phenotype in MHR black-grass. Collectively, these results present a nature-inspired new lead for the development of herbicide synergists to counteract MHR in weeds. This journal is
