[Research progress on pharmacokinetics and pharmacological activities of artesunate].

Artesunate (AS), a famous derivative of the artemisinin, is the basic treatment globally for mild to severe malaria infection due to the prominent advantages such as high efficiency, fast effect, low toxicity and not easy to produce resistance. More and more research reports have shown that AS and its active metabolites dihydroartemisinin (DHA) had various bioactivities in addition to antimalarial activity, attracting researchers to further study its new pharmacological effects in order to explore new use of the old drug. A comprehensive understanding of the pharmacokinetic characteristics of AS will be conducive to the further development of new pharmacological actions and clinical application of AS. Therefore, this paper would review the absorption, distribution, metabolism and excretion of AS in vivo, as well as the pharmacokinetics characteristics of AS and DHA after clinical administration of AS by intravenous (IV), intramuscular (IM), oral or rectal routes. The in vivo process and pharmacokinetic parameters of AS and DHA were compared between healthy volunteers, malaria patients, and special populations (children, women). Meanwhile, the research progress on pharmacological effects of AS and active metabolite DHA such as anti-tumor, anti-inflammatory, anti septic, antiangiogenic, anti-fibrosis and immunoregulation activities would be also reviewed, hoping to provide a theoretical basis for the further development and utilization of AS and its metabolites.

Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors.

Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50=3.3µM, SI >30.3, 12b, EC50=3.5µM, SI >28.6, 10l, EC50=3.9µM, SI >25.6, 12o, EC50=4.5µM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.