Open AccessDesign, synthesis and structure–activity relationships of (±)-isochaihulactone derivatives
Author(s) -
Yu Zhou,
Po Yen Liu,
Kan-Yen Hsieh,
Pei Ling Hsu,
Masuo Goto,
Susan L. MorrisNatschke,
Horng Jyh Harn,
Kuo Hsiung̀ Lee
Publication year - 2017
Publication title -
medchemcomm
Language(s) - English
Resource type - Journals
eISSN - 2040-2511
pISSN - 2040-2503
DOI - 10.1039/c7md00310b
Subject(s) - combinatorial chemistry , chemistry , stereochemistry , computer science
Z-K8 ( 2 ), the racemic form of isochaihulactone ( 1 ), previously showed significant antitumor effects in A549 and LNCaP tumor-bearing mice. In the present study, 17 derivatives of 2 , were designed, synthesized and evaluated for anti-proliferative activity against four human tumor cell lines. All new derivatives exhibited high potency against A549 and P-glycoprotein (P-gp)-overexpressing KBvin. One of our new derivative exhibited greater activity against three tested tumor cells (A549, KB, and KB-VIN) than 2 , and induced cell cycle arrest in the G 2 /M phase. Moreover, SAR conclusions were first established for this series of compounds. Our study clearly identified a structural feature that should be retained for good activity and also a moiety that can tolerate various modifications and, thus, is ideal for further changes.