Design, synthesis, and anticancer activity of three novel palbociclib derivatives.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

Tracking evaluation of "General Provisions of Safety and Health for Writing Boards" / 中国学校卫生

Objective@#To evaluated the application of General Provisions of Safety and Health for Writing Boards(GB 28231-2011), and to provide basis for the revision and improvement of the standard.@*Methods@#From June to October 2018, a questionnaire survey was conducted among 852 people engaged in the evaluation, use and production of writing boards in 8 districts of Beijing, Liaoning and Jiangsu. The contents of the survey include the awareness, implementation of the standard and evaluating the use of various parameters in the standard by personnel from different institutions.@*Results@#The overall awareness ratio of the standard among staffs from health, education and enter prise was 78.26%. For the nominal size of the writing board and the vertical distance between the lower edge and the platform, the reasonableness considered lower by health professionals(62.50%, 37.50%) than that of education professionals(90.00%, 90.00%) and enterprise staffs(90.00%, 90.00%)(P<0.05); For the frequency and reasonableness of the nine parameters such as gloss and adhesion, the perception of each institution were significantly different(P<0.05), with proportion of professionals in health lower than experts in education and enterprise. For the two parameters of color and light resistance, each institution considered the maneuverability was not strong(P>0.05).@*Conclusion@#Propagation and implement is still needed to strengthen comprehension, because different institutions have different understandings towards the standard. There are still some problems waiting to be solved, such as different standard limits, poor enforceability of two parameters which are writing board color and light resistance.