Novel Natural Product-like Caged Xanthones Bearing a Carbamate Moiety Exhibit Antitumor Potency and Anti-Angiogenesis Activity In vivo

Xiaoli Xu, Yue Wu, Mingyang Hu, Xiang Li, Qichao Bao, Jinlei Bian, Qidong You, Xiaojin Zhang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

DDO-6101, a simplified structure obtained from the Garcinia natural product (NP) gambogic acid (GA), has been previously shown to possess high cytotoxicity to a variety of human tumour cell lines. To improve its physicochemical properties and in vivo cytotoxic potency, a series of novel carbamate-bearing derivatives based on DDO-6101 was synthesized and characterized. The structural modifications revealed that the presence of a carbamate moiety was useful for obtaining comparable cytotoxicity and improved aqueous solubility and permeability. 8n, which contains a bipiperidine carbamate moiety, displayed better drug properties and potential in in vivo antitumor activity. In addition, an antitumor mechanistic study suggested that 8n (DDO-6337) inhibited the ATPase activity of Hsp90 (Heat shock protein 90), leading to the inhibition of HIF-1a and ultimately contributing to its anti-angiogenesis and antitumor properties.

Original languageEnglish (US)
Article number35771
JournalScientific reports
Volume6
DOIs
StatePublished - Oct 21 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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