1552272-13-5Relevant academic research and scientific papers
Synthesis and biological evaluation of santacruzamate A and analogs as potential anticancer agents
Liu, Qi,Lu, Wenhua,Ma, Mingzhe,Liao, Jianwei,Ganesan,Hu, Yumin,Wen, Shijun,Huang, Peng
, p. 1109 - 1112 (2015)
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.
Synthesis and biological evaluation of santacruzamate A analogues for anti-proliferative and immunomodulatory activity
Gromek, Samantha M.,deMayo, James A.,Maxwell, Andrew T.,West, Ashley M.,Pavlik, Christopher M.,Zhao, Ziyan,Li, Jin,Wiemer, Andrew J.,Zweifach, Adam,Balunas, Marcy J.
, p. 5183 - 5196 (2016/10/24)
Santacruzamate A (SCA) is a natural product isolated from a Panamanian marine cyanobacterium, previously reported to have potent and selective histone deacetylase (HDAC) activity. To optimize the enzymatic and cellular activity, 40 SCA analogues were synthesized in a systematic exploration of the zinc-binding group (ZBG), cap terminus, and linker region. Two cap group analogues inhibited proliferation of MCF-7 breast cancer cells, with analogous increased degranulation of cytotoxic T cells (CTLs), while one cap group analogue reduced CTL degranulation, indicative of suppression of the immune response. Additional testing of these analogues resulted in reevaluation of the previously reported SCA mechanism of action. These analogues and the resulting structure–activity relationships will be of interest for future studies on cell proliferation and immune modulation.
SANTACRUZAMATE A COMPOSITIONS AND ANALOGS AND METHODS OF USE
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Page/Page column 63, (2014/02/16)
The compositions and methods described herein relate generally to Santacruzamate A compositions and analogs, which, among other features, are useful as histone deacetylase (HDAC) inhibitors.
