Unexpected small molecules as novel SIRT2 suicide inhibitors.

A series of sirtuin inhibitor candidates were assembled based on an intermediate ester (1a) our accidently discovered. After screening and evaluation, several SIRT2 selective inhibitors were identified, which can inhibit all the deacetylation, defatty-acylation and debenzoylation of SIRT2. Among these inhibitors, compound 1e was the best SIRT2 selective inhibitors. The primary study on the inhibitory mechanism indicated that compound 1e may be a suicide inhibitor acting as an irreversible way. Given almost all reported sirtuin inhibitors are non-covalent, sirtuin covalent inhibitors are still need to be developed. These findings will facilitate for further development of SIRT2 selective and suicide inhibitors.

A Series of Novel HDAC Inhibitors with Anthraquinone as a Cap Group.

Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displayed the comparable inhibition in enzymatic activity and cell proliferation than that of Vorinostat (SAHA). Notably, compound 4b showed certain selectivity of antiproliferative effects on cancer cell lines over non-cancer cell lines.

The mimics of Nε-acyl-lysine derived from cysteine as sirtuin inhibitors.

Sirtuin inhibitors as physiological research tools and therapeutic potentials have caught many attentions in last decades. The mimics of acyl lysine have been approved to be a very efficient strategy for development of mechanism-based sirtuin inhibitors. In current study, a novel scaffold of l-S-(3-carboxamidopropyl) cysteine (l-CAPC) has been exploited for design and synthesis of sirtuin inhibitors. As a result, the mimics of Nε-acyl-lysine derived from cysteine including small molecules (5a-m) and peptides (9a-m) have been synthesized. Among these, the peptides 9g and 9h were found to be the most inhibitory potency and selectivity against SIRT2.

The effect of training orthopedic nurse specialists in Jiangsu Province of China.

BACKGROUND: The training of orthopedic nurse specialists is gradually increasing in China, but the effect of the training, namely the specialized nursing work carried out by them upon returning to work after training, is unknown. This study aimed to further our understanding of the effect of training orthopedic nurse specialists and provide a basis for improving the training program. METHODS: A total of 201 clinical nurse specialists who graduated from the training base of orthopedic nurse specialists in the Jiangsu Province were interviewed via a self-made questionnaire. RESULTS: All orthopedic nurse specialists completed a series of specialized nursing work after returning to their posts. In particular, the clinical nurse specialists with senior professional titles participated in more specialized nursing work projects, such as continuous improvement of orthopedic nursing quality, and so on. The influence of having attained different educational levels on the specialized nursing work of orthopedic nurse specialists was not significant. CONCLUSIONS: The orthopedic nurse specialists carried out a series of specialized nursing work after returning to their posts, which not only helps to improve the quality of orthopedic nursing, but also assists in promoting the popularization and homogenization of new knowledge and skills in orthopedic nursing in the Jiangsu Province.

N ɛ -acetyl lysine derivatives with zinc binding groups as novel HDAC inhibitors.

HDAC inhibitors have been developed very rapidly in clinical trials and even in approvals for treating several cancers. However, there are few reported HDAC inhibitors designed from N ɛ -acetyl lysine. In the current study, we raised a novel design, which concerns N ɛ -acetyl lysine derivatives containing amide acetyl groups with the hybridization of ZBG groups as novel HDAC inhibitors.