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Design, Synthesis and Structure-Activity Relationships of (±)-Isochaihulactone Derivatives.
MedChemComm 2017
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 G2 /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.
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