94136-35-3Relevant academic research and scientific papers
Novel alkoxyamide-based histone deacetylase inhibitors reverse cisplatin resistance in chemoresistant cancer cells
Asfaha, Yodita,Schrenk, Christian,Alves Avelar, Leandro A.,Lange, Friedrich,Wang, Chenyin,Bandolik, Jan J.,Hamacher, Alexandra,Kassack, Matthias U.,Kurz, Thomas
supporting information, (2019/12/11)
Although histone deacetylase inhibitors (HDACi) have shown promising antitumor effects in specific types of blood cancer, their effects on solid tumors are limited. Previously, we developed LMK235 (5), a class I and class IIb preferential HDACi with chemosensitizing effects on breast cancer, ovarian cancer and HNSCC. Based on its promising effects on solid tumor cells, we modified the cap group of 5 to improve its anticancer activity. The tri- and dimethoxy-phenyl substituted compounds 13a and 13d turned out to be the most potent HDAC inhibitors of this study. The isoform profiling revealed a dual HDAC2/HDAC6 inhibition profile, which was confirmed by the acetylation of α-tubulin and histone H3 in Cal27 and Cal27CisR. In combination with cisplatin, both compounds enhanced the cisplatin-induced cytotoxicity via caspase-3/7 activation. The effect was more pronounced in the cisplatin resistant subline Cal27CisR. The pretreatment with 13d resulted in a complete resensitisation of Cal27CisR with IC50 values in the range of the parental cell line. Therefore, 13d may serve as an epigenetic tool to analyze and modulate the cisplatin resistance of solid tumors.
Alkoxyurea-Based Histone Deacetylase Inhibitors Increase Cisplatin Potency in Chemoresistant Cancer Cell Lines
Stenzel, Katharina,Hamacher, Alexandra,Hansen, Finn K.,Gertzen, Christoph G. W.,Senger, Johanna,Marquardt, Viktoria,Marek, Linda,Marek, Martin,Romier, Christophe,Remke, Marc,Jung, Manfred,Gohlke, Holger,Kassack, Matthias U.,Kurz, Thomas
, p. 5334 - 5348 (2017/07/22)
The synthesis and biological evaluation of potent hydroxamate-based dual HDAC1/6 inhibitors with modest HDAC6 preference and a novel alkoxyurea connecting unit linker region are described. The biological studies included the evaluation of antiproliferative effects and HDAC inhibitory activity in the human ovarian cancer cell line A2780, the human squamous carcinoma cell line Cal27, and their cisplatin resistant sublines A2780CisR and Cal27CisR. The three most potent compounds 1g-i showed IC50 values in the low μM and sub-μM range. 1g-i revealed low nM IC50 values for HDAC6 with up to 15-fold preference over HDAC1, >3500-fold selectivity over HDAC4, and >100-fold selectivity over HDAC8. Furthermore, their ability to enhance cisplatin sensitivity was analyzed in Cal27 and Cal27CisR cells. Notably, a 48 h preincubation of 1g-i significantly enhanced the antiproliferative effects of cisplatin in Cal27 and Cal27CisR. 1g-i interacted synergistically with cisplatin. These effects were more pronounced for the cisplatin resistant subline Cal27CisR.
Potent inducers of terminal differentiation and method of use thereof
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, (2008/06/13)
This invention is directed to compounds having the structure: STR1 wherein R1 and R2 are independently the same as or different from each other; when R1 and R2 are the same, each is a substituted or unsubstitute
Potent inducers of terminal differentiation and methods of use thereof
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, (2008/06/13)
The present invention provides the compound having the structure: STR1 wherein each of R1 and R2 are independently the same as or different from each other; when R1 and R2 are the same, each is a substituted or
Artificial siderophores. 2. Syntheses of trihydroxamate analogues of rhodotorulic acid and their biological iron transport capabilities in Escherichia coli
Lee,Miller,Prody,Neilands
, p. 323 - 327 (2007/10/02)
Tris[(acetylhydroxyamino)alkyl] isocyanurates 2a-c were synthesized from α,ω-dibromoalkanes in four steps. The alkylation of the bromides with O-benzyl-N-[(trichloroethoxy)carbonyl]hydroxylamine in the presence of DBU gave N-alkylation products 7a-c. The
