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Some rare indigo derivatives have been known for a long time to be photochromic upon irradiation with red light, which should be advantageous for many applications. However, the absence of strategies to tune their thermal halflives by modular molecular design as well as the lack of proper synthetic methods to prepare a variety of such molecules from the parent indigo dye have so far precluded their use. In this work, several synthetic protocols for N-functionalization have been developed and a variety of N-alkyl and N-aryl indigo derivatives have been prepared. By installation of electron-withdrawing substituents on the N-aryl moieties, the thermal stability of the Z-isomers could be enhanced while maintaining the advantageous photoswitching properties upon irradiation with red light (660 nm LED). Both experimental data and computational results suggest that the ability to tune thermal stability without affecting the dye's absorption maxima originates from the twisted geometry of the N-aryl groups. The new indigo photoswitches reported are expected to have a large impact on the development of optical methods and applications in both life and material sciences. [ABSTRACT FROM AUTHOR]

A nickel-catalyzed cross-coupling reaction between N-sulfonyl aziridines and organozinc reagents is reported. The catalytic system comprises an inexpensive and air-stable Ni(II) source and dimethyl fumarate as ligand. Regioselective synthesis of β-substituted aniines is possible under mild and functional-group-tolerant con- ditions. The stereoselectivity of the reaction is consistent with a stereoconvergent mechanism wherein the sulfona- mide directs C-C bond formation. [ABSTRACT FROM AUTHOR]

A Ni-catalyzed reductive cross-coupling of styrenyl aziridines with aryl iodides is reported. This reaction proceeds by a stereoconvergent mechanism and is thus amenable to asymmetric catalysis using a chiral bioxazoline ligand for Ni. The process allows facile access to highly enantioenriched 2-arylphenethylamines from racemic aziridines. Multivariate analysis revealed that ligand polarizability, among other features, influences the observed enantioselectivity, shedding light on the success of this emerging ligand class for enantioselective Ni catalysis. [ABSTRACT FROM AUTHOR]

Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4. [ABSTRACT FROM AUTHOR]

NBM-T-L-BMX-OS01 (BMX) was derived from the semisynthesis of osthole, isolated from Cnidium monnieri (L.) Cuss., and was identified to be a potent inhibitor of HDAC8. This study shows that HDAC8 is highly expressed in the pancreas and the brain. The function of HDAC8 in the brain has not been adequately studied. Because BMX enhances neurite outgrowth and cAMP response element-binding protein (CREB) activation, the effect of BMX on neural plasticity such as learning and memory is examined. To examine declarative and nondeclarative memory, a water maze, a passive one-way avoidance task, and a novel object recognition task were performed. Results from the water maze revealed that BMX and suberoylanilide-hydroxamic-acid-(SAHA-) treated rats showed shorter escape latency in finding the hidden platform. The BMX-treated animals spent more time in the target quadrant in the probe trial performance. An analysis of the passive one-way avoidance results showed that the BMX-treated animals stayed longer in the illuminated chamber by 1 day and 7 days after footshock. The novel object recognition task revealed that the BMX-treated animals showed a marked increase in the time spent exploring novel objects. Furthermore, BMX ameliorates scopolamine-(Sco-) induced learning and memory impairment in animals, indicating a novel role of BMX in learning and memory. [ABSTRACT FROM AUTHOR]

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NB M-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells ( MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50 ranging from 8.5 to 10.3 μ M.Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NB M-HD-1. After NB M-HD-1 treatment for 1-4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NB M-HD-1 in regulating cell cycle regulators. Treatment with NB M-HD-1, p21(Waf1/Cip1) gene expression hadmarkedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NB MHD- 1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NB M-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NB M-HD- 1, is a novel and potent HDACi with anticancer activity in vitro and in vivo. [ABSTRACT FROM AUTHOR]