Synthesis and Antitumor Activity of Bis(hydroxymethyl)propionate Analogs of Pterostilbene in Cisplatin-resistant Human Oral Cancer Cells

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2018 Jun 18

PMID 29908756

Citations 7

Authors

Min-Tsang Hsieh

Li-Jiau Huang

Tian-Shung Wu

Hui-Yi Lin

Susan L Morris-Natschke

Kuo-Hsiung Lee

Sheng-Chu Kuo

Affiliations

Soon will be listed here.

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.

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