RESUMO
Cisplatin is a chemotherapy drug that causes permanent hearing loss by injuring cochlear hair cells. The mechanisms that initiate injury are not fully understood, but mitochondria have emerged as potential mediators of hair cell cytotoxicity. Using in vivo live imaging of hair cells in the zebrafish lateral-line organ expressing a genetically encoded indicator of cumulative mitochondrial activity, we first demonstrate that greater redox history increases susceptibility to cisplatin. Next, we conducted time-lapse imaging to understand dynamic changes in mitochondrial homeostasis and observe elevated mitochondrial and cytosolic calcium that surge prior to hair cell death. Furthermore, using a localized probe that fluoresces in the presence of cisplatin, we show that cisplatin directly accumulates in hair cell mitochondria, and this accumulation occurs before mitochondrial dysregulation and apoptosis. Our findings provide evidence that cisplatin directly targets hair cell mitochondria and support that the mitochondria are integral to cisplatin cytotoxicity in hair cells.
RESUMO
A versatile protocol for the direct thiolation of an inert sp2 C-H bond is presented via a catalytic amount of copper catalysis, by switching related Brønsted bases and regulating the reaction time, and the corresponding mono- and dithiolation products can be obtained selectively in moderate to good yields. The reaction exhibits a relatively broad substrate scope and a good functional group tolerance, even with different heterocyclic amides and alkyl thiols.
RESUMO
Here, we present an unprecedented pathway to α-sulfenylated carbonyl compounds from commercially available thiols and universally employed TEMPO and its analogues, which act as C3 synthons through skeletal rearrangement under simple and metal-free conditions. Mechanism studies suggest that this reaction involves a consecutive radical oxidation and cation coupling process. TEMPO analogues and thiols serve as oxidants and reductive reagents, respectively, along the radical process, while in the coupling process, the former ones afford C3 synthons to couple with related sulfur sources.
RESUMO
An efficient and practical methodology to obtain α-thio-ß-dicarbonyl compounds was presented under alkaline conditions via potassium iodide (KI) catalysis; various symmetrical/unsymmetrical 1,3-dicarbonyl compounds were obtained under an aerobic atmosphere in moderate to excellent yields, with good functional group tolerance. Notably, a widely used anti-inflammatory drug butazodine could be modified with our protocol, even on a gram scale.
RESUMO
An efficient, environmentally benign and unprecedented synthesis of various α-sulfenylated amides/esters has been developed under oxygen atmosphere. The reaction shows good functional group tolerance and excellent chemo/regioselectivity. All the desired products were obtained in moderate to excellent yields, even on the gram scale. Practically, the related α-thiol Weinreb amide can be readily transferred to a series of prospective compounds, and selenium atom can be introduced to the α-sites of the amides in high yields.