Abstract
Aim: Class I histone deacetylases (HDACs) are considered to be promising anticancer targets, but selective inhibition of class I HDAC isoforms remains a challenge. Methods & results: Previously, we obtained a selective class I HDAC inhibitor 9 based on a macrocyclic HDAC inhibitor Romidpesin. As our continuous efforts, a library of novel cyclicdepsipeptides based on 9 was established using a convergent synthesis strategy. The most active compounds 10, 16 and 19 selectively inhibit class I HDACs and exhibit promising nanomolar antiproliferative activities against several cancer cell lines with excellent selectivity toward cancer cells over normal cells. Besides, compound 10 demonstrates excellent antitumor effects in human prostate carcinoma PC3 xenograft models with no observed toxicity. Conclusion: These cyclicdepsipeptides show great therapeutic potential as novel anticancer agents for clinical translation.
Original language | English (US) |
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Pages (from-to) | 311-323 |
Number of pages | 13 |
Journal | Future Medicinal Chemistry |
Volume | 12 |
Issue number | 4 |
Early online date | Nov 29 2019 |
DOIs | |
State | Published - Feb 2020 |
Keywords
- antitumor
- class I histone deacetylases
- cyclic depsipeptides
- inhibitor
- structure-activity relationship
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery