Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, United States.
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
ACS Chem Biol. 2022 Jul 15;17(7):1658-1664. doi: 10.1021/acschembio.2c00240. Epub 2022 Jun 9.
A high-throughput cell-based screen identified redox-active small molecules that produce a period lengthening of the circadian rhythm. The strongest period lengthening phenotype was induced by a phenazine carboxamide (VU661). Comparison to two isomeric benzquinoline carboxamides (VU673 and VU164) shows the activity is associated with the redox modulating phenazine functionality. Furthermore, ex vivo cell analysis using optical redox ratio measurements shows the period lengthening phenotype to be associated with a shift to the NAD/FAD oxidation state of nicotinamide and flavine coenzymes.
一种高通量基于细胞的筛选方法鉴定出了具有氧化还原活性的小分子，这些小分子能使生物钟节律的周期延长。其中，苯并喹啉羧酰胺（VU661）诱导出的周期延长表型最强。与两种非对映异构体苯并喹啉羧酰胺（VU673 和 VU164）的比较表明，这种活性与氧化还原调节苯并嗪功能有关。此外，使用光学氧化还原比测量的离体细胞分析表明，周期延长表型与烟酰胺和黄素辅酶的 NAD/FAD 氧化状态的转变有关。
