35340-63-7Relevant articles and documents
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.
supporting information, 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 46, (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.
Structural effects of N-aromatic acyl-amino acid conjugates on their deconjugation in the cecal contents of rats: Implication in design of a colon-specific prodrug with controlled conversion rate at the target site
Kong, Hyesik,Kim, Hyunjeong,Do, Heejeong,Lee, Yonghyun,Hong, Sungchae,Yoon, Jeong-Hyun,Jung, Yunjin,Kim, Young Mi
experimental part, p. 343 - 354 (2012/04/10)
N-aromatic acyl-amino acid conjugates possess a colon-targeted property, implying that such conjugates are stable and are not absorbable until reaching the large intestine in which they are microbially converted (hydrolysed) to the parent drugs that are therapeutically active. To investigate the structural effect of N-aromatic acyl-amino acid conjugates on the large intestinal deconjugation, the hydrolysis of various N-aromatic acyl-amino acid conjugates was examined in the cecal contents. On incubation of conjugates with glycine,d or/andl forms of alanine or phenylalanine in the cecal contents, the conjugates withd amino acids were not hydrolysed. The other conjugates are susceptible to the hydrolysis, the rates of which decreased as the size of the substituent on the 2-position of the amino acids increased. The conjugates with alkyl analogs (2-4 carbons) of glycine and taurine were resistant to the hydrolysis, while taurine- and glycine-conjugates were hydrolysed effectively. The hydrolysis of N-aromatic acyl-glycine conjugates was enhanced by para-substitution of electron withdrawing groups on the aromatic acyl moiety and vice versa for electron-donating groups. While a methyl, methoxy or chloro group on the ortho-position retarded the hydrolysis, a hydroxyl group on the position accelerated it. Our data may provide useful information for the design of a colon-specific prodrug with controlled conversion rate in the large intestine.
