53339-53-0Relevant articles and documents
Thiol-responsive pro-fluorophore labeling: Synthesis of a pro-fluorescent labeled oligonucleotide for monitoring cellular uptake
Akai, Shoji,Ohta, Takayuki,Ono, Akira,Saneyoshi, Hisao,Yamamoto, Yuta
, (2020)
Pro-fluorescent labeled oligonucleotides are potential alternative tools to classical fluorescently labeled oligonucleotides for monitoring cellular uptake. Here, we report the design and synthesis of a thiol-responsive pro-fluorophore labeled oligonucleotide, and its fluorescence responsivity to glutathione in the test tube and live cells.
Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
, (2020/11/24)
Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.
Reduction-responsive amphiphilic antitumor pharmic conjugate and preparation method and application thereof
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Paragraph 0040; 0044-0045; 0054, (2019/10/22)
The invention relates to a reduction-responsive amphiphilic antitumor pharmic conjugate and a preparation method and application thereof. The reduction-responsive amphiphilic antitumor pharmic conjugate has a molecular structural formula shown in a formula I, wherein ROH is a hydrophobic antitumor drug; n is 5-1000. The provided prodrug can achieve targeted drug delivery, which not only retains the advantages of a nano-drug-loading system, but also exhibits the characteristic of specific degradation of a disulfide bond at a tumor site. Compared with conventional connecting arms such as 2,2'-dithiodiacetic acid and 3,3'-dithiodipropionic acid, the anticancer drug in an original drug molecule form can be obtained without further hydrolysis.