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Professor Hui Wang’s Team from School of Public Health reveals new Artemisinin derivates against ovarian cancer
Published:2016-12-20 Hits:247次

        There is an increasing interest in developing natural product anticancer agents that have better efficacy and safety profiles than conventional synthetic compounds. Artemisinin compounds, clinically well-established anti-malarial traditional medicines, have recently drawn people’s attention as anticancer agents for their clinical safety profiles and broad anticancer efficacy. However, their therapeutic potencies are limited by low solubility and poor bioavailability.
  A team of scientists led by Dr. Hui Wang from School of Public health, Shanghai Jiao Tong University School of Medicine found a novel Artemisinin derivate possesses marked in-vitro and in-vivo antitumor activity against ovarian cancer. Through a pharmacophore hybridization strategy, they synthesized ARS-drug conjugates, in which the marketed chemotherapeutic agents chlorambucil, melphalan, flutamide, aminoglutethimide, and doxifluridine, were separately bonded to Dihydroartemisinin (DHA) through various linkages. Of these, the artemisinin-melphalan conjugate, ARS4, exhibited most toxicity to human ovarian cancer cells but had low cytotoxicity to normal cells. ARS4 inhibited the growth and proliferation of ovarian cancer cells and resulted in S-phase arrest, apoptosis, and inhibition of migration; these effects were stronger than those of its parent drugs, DHA and melphalan. In mice, ARS4 inhibits localized growth of ovarian cancer cells and intraperitoneal dissemination and metastasis without appreciable host toxicity. Thus, for patients with ovarian cancer, ARS4 is a promising chemotherapeutic agent.
  This work was published in Ebiomedicine on December, 2016, as a research article entitled“Preclinical Efficacy and Safety Assessment of Artemisinin-Chemotherapeutic Agent Conjugates for Ovarian Cancer”. This study was funded by Ministry of Science and Technology of China, the National Natural Science Foundation of China, Chinese Academy of Sciences and the Science and Technology Commission of Shanghai Municipality.


  

 Novel Artemisinin-Melphalan Conjugate ARS4 for Ovarian Cancer Therapy
  A. The design strategy and chemical structure of ARS4. B-C.ARS4 inhibits tumor growth (B) and metastasis (C) in mice bearing xenografted ovarian tumor cells.
 

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