Issue 2, 2015

Synthesis and biological evaluation of santacruzamate A and analogs as potential anticancer agents

Abstract

Santacruzamate A, a recently discovered natural product from a Panamanian marine cyanobacterium Symploca sp., features a similar structure to the clinically used histone deacetylase (HDAC) inhibitor vorinostat (SAHA). We have synthesized the natural product and a small set of analogues for SAR studies. To our surprise, the synthetic natural product santacruzamate A (1a) and the analogues did not show an obvious inhibition even at 2 μM in HDAC enzyme assays while the IC50 value was 0.12 nM in the original report. However, a novel compound, 5, containing a terminal thiourea motif was found to inhibit the growth of malignant cells at submicromolar concentrations. Moreover, 5 was not cytotoxic to normal human colonic epithelial cells CCD841, suggesting that its cytotoxicity was specific to cancer cells. Further investigation indicated that the compound induced apoptosis, affected cell cycle progression and increased ROS production. We believe its mechanism of action is unrelated to HDAC inhibition and the original activity reported for santacruzamate needs to be reevaluated.

Graphical abstract: Synthesis and biological evaluation of santacruzamate A and analogs as potential anticancer agents

Supplementary files

Article information

Article type
Communication
Submitted
05 Nov 2014
Accepted
26 Nov 2014
First published
26 Nov 2014

RSC Adv., 2015,5, 1109-1112

Author version available

Synthesis and biological evaluation of santacruzamate A and analogs as potential anticancer agents

Q. Liu, W. Lu, M. Ma, J. Liao, A. Ganesan, Y. Hu, S. Wen and P. Huang, RSC Adv., 2015, 5, 1109 DOI: 10.1039/C4RA13889A

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