Synthesis and antitumor activity of bis(hydroxymethyl)propionate analogs of pterostilbene in cisplatin-resistant human oral cancer cells

Min Tsang Hsieh, Li Jiau Huang, Tian Shung Wu, Hui Yi Lin, Susan L. Morris-Natschke, Kuo Hsiung Lee, Sheng Chu Kuo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The aim of this study was to develop a new drug substance with low toxicity and effective inhibitory activity against cisplatin-resistant oral cancer. The naturally produced pterostilbene was selected as the lead compound for design and synthesis of a series of bis(hydroxymethyl)propionate-based prodrugs. All derivatives were screened for antiproliferative effects against the cisplatin-resistant oral squamous (CAR) cell line and the results indicated that several compounds demonstrated superior inhibitory activity compared with pterostilbene and resveratrol. Among them, the most promising compound, 12, was evaluated for in vivo antitumor activity in a CAR xenograft nude mouse model. Obvious antitumor activity was observed at the lowest oral dose (25 mg/kg/day). Increasing the dose of 12 to 100 mg/kg/day reduced the tumor size to 22% of the control group. Based on these findings as well as the extremely low toxicity seen in the in vivo studies, we believe that compound 12 could serve as a new lead for further development.

Original languageEnglish
Pages (from-to)3909-3916
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number14
DOIs
Publication statusPublished - 2018 Aug 7

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis and antitumor activity of bis(hydroxymethyl)propionate analogs of pterostilbene in cisplatin-resistant human oral cancer cells'. Together they form a unique fingerprint.

Cite this