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Chem Biol Drug Des. 2013 Sep;82(3):307-16. doi: 10.1111/cbdd.12154. Epub 2013 Jun 29.

Synthesis and cytotoxic evaluation of acylated brefeldin a derivatives as potential anticancer agents.

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  • 1College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310014, China.


Brefeldin A has attracted considerable attention because of its potential function in cancer prevention. However, its therapeutic use is limited by its poor bioavailability. The modifications on brefeldin A were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule. In this study, we report the selective acylation of brefeldin A under mild conditions and the preparation of a series of monoacylated and diacylated brefeldin A derivatives. Their cytotoxicity, antitumor activity against TE-1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated. Brefeldin A 7-O-benzoate, brefeldin A 4,7-O-dibenzoate, and brefeldin A 7-O-biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0.39, 0.46, and 0.50 μm, respectively. Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. Our results may serve as a basis for the development of novel potential anticancer agents from brefeldin A derivatives.

© 2013 John Wiley & Sons A/S.


acylation; antiproliferative activity; brefeldin A derivatives; molecular modeling; prodrug

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