1137735-74-0Relevant articles and documents
Radical-Mediated Thiol-Ene Strategy: Photoactivation of Thiol-Containing Drugs in Cancer Cells
Sun, Shuang,Oliveira, Bruno L.,Jiménez-Osés, Gonzalo,Bernardes, Gon?alo J. L.
, p. 15832 - 15835 (2018/11/10)
Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer. Described herein is a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide, and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, it is shown that the activity of histone deacetylase inhibitor largazole can be switched off when stapled, but selectively switched on within cancer cells when irradiated with non-phototoxic light.
Modular synthesis and biological activity of pyridyl-based analogs of the potent Class i Histone Deacetylase Inhibitor Largazole
Clausen, Dane J.,Smith, William B.,Haines, Brandon E.,Wiest, Olaf,Bradner, James E.,Williams, Robert M.
, p. 5061 - 5074 (2015/08/03)
The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein.
Biological evaluation of new largazole analogues: Alteration of macrocyclic scaffold with click chemistry
Li, Xianlin,Tu, Zhenchao,Li, Hua,Liu, Chunping,Li, Zheng,Sun, Qiao,Yao, Yiwu,Liu, Jinsong,Jiang, Sheng
supporting information, p. 132 - 136 (2013/03/13)
We report the design, synthesis, and biological evaluation of a new series of largazole analogues in which a 4-methylthiazoline moiety was replaced with a triazole and tetrazole ring, respectively. Compound 7 bearing a tetrazole ring was identified to show much better selectivity for HDAC1 over HDAC9 than largazole (10-fold). This work could serve as a foundation for further exploration of selective HDAC inhibitors using a largazole molecular scaffold.