Design, synthesis and biological evaluation of selective survivin inhibitors

Min Xiao, Yi Xue, Zhongzhi Wu, Zi Ning Lei, Jin Wang, Zhe Sheng Chen, Wei Li

Research output: Contribution to journalArticle

Abstract

The differential distribution between cancer cells and normal adult tissues makes survivin a very attractive cancer drug target. We have previously reported a series of novel selective survivin inhibitors with the most potent compound MX106 reaching nanomolar activity in several cancer cell lines. Further optimization of the MX106 scaffold leads to the discovery of more potent and more selective survivin inhibitors. Various structural modifications were synthesized and their anticancer activities were evaluated to determine the structure activity relationships for this MX106 scaffold. In vitro anti-proliferative assays using two human melanoma cell lines showed that several new analogs have improved potency compared to MX106. Very interestingly, these new analogs generally showed significantly higher potency against P-glycoprotein overexpressed cells compared with the corresponding parental cells, suggesting that these compounds may strongly sensitize tumors that have high expressions of the P-glycoprotein drug efflux pumps. Western blotting analysis confirmed that the new MX106 analogs maintained their mechanism of actions by selectively suppressing survivin expression level among major inhibitors of apoptotic proteins and induced strong apoptosis in melanoma tumor cells.

Original languageEnglish (US)
Pages (from-to)82-100
Number of pages19
JournalJournal of Biomedical Research
Volume33
Issue number2
DOIs
StatePublished - Jan 1 2019

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Cells
P-Glycoprotein
Scaffolds
Tumors
Neoplasms
Melanoma
Cell Line
Pharmaceutical Preparations
Assays
Structure-Activity Relationship
Pumps
Tissue
Apoptosis
Western Blotting
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Design, synthesis and biological evaluation of selective survivin inhibitors. / Xiao, Min; Xue, Yi; Wu, Zhongzhi; Lei, Zi Ning; Wang, Jin; Chen, Zhe Sheng; Li, Wei.

In: Journal of Biomedical Research, Vol. 33, No. 2, 01.01.2019, p. 82-100.

Research output: Contribution to journalArticle

Xiao, Min ; Xue, Yi ; Wu, Zhongzhi ; Lei, Zi Ning ; Wang, Jin ; Chen, Zhe Sheng ; Li, Wei. / Design, synthesis and biological evaluation of selective survivin inhibitors. In: Journal of Biomedical Research. 2019 ; Vol. 33, No. 2. pp. 82-100.
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