33588-54-4Relevant articles and documents
Indirubin Derivatives as Dual Inhibitors Targeting Cyclin-Dependent Kinase and Histone Deacetylase for Treating Cancer
An, Jianxiong,Cao, Zhuoxian,Gu, Zhicheng,He, Bin,Li, Yan,Li, Yongjun,Lin, Hening,Lin, Shuxian,Liu, Ting,Wang, Jie,Wang, Pan,Yang, Fenfen,Zhao, Yonglong
, p. 15280 - 15296 (2021/10/25)
To utilize the unique scaffold of a natural product indirubin, we herein adopted the strategy of combined pharmacophores to design and synthesize a series of novel indirubin derivatives as dual inhibitors against cyclin-dependent kinase (CDK) and histone deacetylase (HDAC). Among them, the lead compound 8b with remarkable CDK2/4/6 and HDAC6 inhibitory activity of IC50 = 60.9 ± 2.9, 276 ± 22.3, 27.2 ± 4.2, and 128.6 ± 0.4 nM, respectively, can efficiently induce apoptosis and S-phase arrest in several cancer cell lines. In particular, compound 8b can prevent the proliferation of a non-small-cell lung cancer cell line (A549) through the Mcl-1/XIAP/PARP axis, in agreement with the unique modes of action of the combined agents of HDAC inhibitors and CDK inhibitors. In an A549 xerograph model, compound 8b showed significant antitumor efficacy correlated with its dual inhibition. Our data demonstrated that compound 8b as a single agent could be a promising drug candidate for cancer therapy in combination with CDK and HDAC inhibitors.
Araf51 with improved transglycosylation activities: One engineered biocatalyst for one specific acceptor
Pennec, Alizé,Daniellou, Richard,Loyer, Pascal,Nugier-Chauvin, Caroline,Ferrières, Vincent
, p. 50 - 55 (2015/02/19)
A random mutagenesis of the arabinofuranosyl hydrolase Araf51 has been run in order to have access to efficient biocatalysts for the synthesis of alkyl arabinofuranosides. The mutants were selected on their ability to catalyze the transglycosylation reaction of p-nitrophenyl α-l-arabinofuranoside (pNP-Araf) used as a donor and various aliphatic alcohols as acceptors. This screening strategy underlined 5 interesting clones, each one corresponding to one acceptor. They appeared to be much more efficient in the transglycosylation reaction compared to the wild type enzyme whereas no self-condensation or hydrolysis products could be detected. Moreover, the high specificity of the mutants toward the alcohols for which they have been selected validates the screening process. Sequence analysis of the mutated enzymes revealed that, despite their location far from the active site, the mutations affect significantly the kinetics properties as well as the substrate affinity of these mutants toward the alcohol acceptors in the transglycosylation reaction.
Indole-3-piperazinyl derivatives: Novel chemical class of 5-HT6 receptor antagonists
Nirogi, Ramakrishna V.S.,Deshpande, Amol D.,Kambhampati, Ramasastri,Badange, Rajesh Kumar,Kota, Laxman,Daulatabad, Anand V.,Shinde, Anil K.,Ahmad, Ishtiyaque,Kandikere, Vishwottam,Jayarajan, Pradeep,Dubey
scheme or table, p. 346 - 349 (2011/02/28)
N1-Arylsulfonyl-3-piperazinyl indole derivatives were designed and identified as a novel class of 5-HT6 receptors ligands. All the compounds have high affinity and antagonist activity towards 5-HT6 receptor. The compound 7a (Ki = 3.4 nM, functional assay IC 50 = 310 nM) shows enhanced cognitive effect when tested in NORT and Morris water maze models. Synthesis, SAR and PK profile of these novel compounds constitute the subject matter of this Letter.
