Search Results (2)

Nur77 is an orphan nuclear receptor that participates in the occurrence and development of a variety of tumors. Many agonists of Nur77 have been reported to have significant anticancer effects. Our previous studies have found that the introduction of bicyclic aromatic rings, such as naphthalyl and quinoline groups, into the N′-methylene position of indoles’ Nur77 modulators can effectively improve the anti-tumor activity of the target compounds. Following our previous studies, a series of novel 1-(2-(6-methoxynaphthalen-2-yl)-6-methylnicotinoyl)-4-substituted semicarbazide/thiosemicarbazide derivatives 9a–9w were designed and synthesized in four steps from 6-methoxy-2-acetonaphthone and N-dimethylformamide dimethylacetal. All compounds were characterized by ¹H-NMR, ¹³C-NMR and HRMS, and their anti-tumor activity on various cancer cell lines such as A549, HepG2, HGC-27, MCF-7 and HeLa are also evaluated. From the series of compounds, 9h exhibited the most potent anti-proliferative activity against several cancer cells. Colony formation and cell cycle experiments showed that compound 9h inhibited cell growth and arrested the cell cycle. Additionally, 9h leads to the cleavage of PARP. We initially explored the mechanism of 9h-induced apoptosis and found that compound 9h can upregulate Nur77 expression and triggered Nur77 nuclear export, indicating the occurrence of Nur77-mediated apoptosis. These results suggested that 9h may be a promising anti-tumor leading compound for the further research. Full article

Inspired by the active site structures of lactate racemase and recently reported sulphur–carbon–sulphur (SCS) nickel pincer complexes, a series of scorpion-like SCS nickel pincer complexes with an imidazole tail and asymmetric claws was proposed and examined computationally as potential catalysts for the asymmetric transfer hydrogenation of 1-acetonaphthone. Density functional theory calculations reveal a proton-coupled hydride transfer mechanism for the dehydrogenation of (R)-(+)-1-phenyl-ethanol and the hydrogenation of 1-acetonaphthone to produce (R)-(+)-1-(2-naphthyl)ethanol and (S)-(−)-1-(2-naphthyl)ethanol. Among all proposed Ni complexes, 1_Ph is the most active one with a rather low free energy barrier of 24 kcal/mol and high enantioselectivity of near 99% enantiomeric excess (ee) for the hydrogenation of prochiral ketones to chiral alcohols. Full article