Synthesis and antitumor activity of 1, 2-benzothiazines imidazolo ［1, 2-b］［1, 3, 4］ triazazole derivatives / 中国药科大学学报

@#In this study, triazazole moiety was introduced to piroxicam, a nonsteroidal anti-inflammatory drug, via bioisosterism to produce eight target analogs, which were structurally characterized by 1H NMR and MS. These target compounds were tested for inhibitory activities on pancreatic cancer cell(Capan-1)and leukemia cell(L1210). The results showed that compound 6b had good antiproliferative activity against Capan-1 cells(IC50=3. 6±0. 5 μmol/L); while compound 6a had good antiproliferative activity against L1210 cells(IC50=1. 8±0. 2 μmol/L), indicating that the introduction of the imidazolo［1, 2-b］［1, 3, 4］triazazole moiety could be helpful to improve the antitumor activity of these compounds.

Synthesis and anti-tumor activity of ginsenoside Rh_2 caprylic acid monoester / 中国中药杂志

Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.

Design, synthesis and evaluation of a novel MEK protein inhibitors / 药学学报

This study was conducted to design and synthetize highly efficient, specific, non-resistant small MEK inhibitors. Based on active small molecules which have been reported, we studied the action mode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designed novel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumor activities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT method in vitro. The structure of 10 new small molecules has been determined with 1H NMR and 13C NMR. The compounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity, and the compounds 2, 9 showed cell selectivity in killing tumor.

Improvement of Synthetic Technology of Nateglinide / 中国药房

OBJECTIVE: To improve the synthetic technology of nateglinide so as to increase yield and promote industrial production.METHODS: The improvement was conducted from aspects of reagent,catalyst,crystal form transformation etc in which the sodium hydride reported in literature was substituted by sodium hydrate in cis-trans transformation,and phosphorus trichloride or phosphorus pentachloride was substituted by thionyl chloride for the chlorination,and PtO2 or Raney Ni was substituted by RuNiAlC as catalytic agent.In H form crystal form transformation,fine seed-crystal was obtained by low temperature crushing,which was added with seed-crystal to induce crystallization to obtain H form crystal.The structure of the crystal form of the product obtained using the improved technology was characterized and its yield was computed.RESULTS: The crystal form characterization results demonstrated that the product was H form crystal and its yield reached 72%,higher than that reported in literature(50%).CONCLUSION: The improved technology of nateglinide contributed to the increase of its yield;Therefore,this technology is suitable for industrial production.