33588-54-4Relevant academic research and scientific papers
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.
Indoxyl-based umpolung strategy for the synthesis of unsymmetrical 3,3′-biindoles
Guo, Jing,Weng, Jiang,Huang, Gong-Bin,Huang, Lin-Jie,Chan, Albert S.C.,Lu, Gui
, p. 5493 - 5496 (2016/11/19)
3,3′-Bisindoles are known to be important structural motifs found in bioactive natural products, pharmaceuticals, and functional materials. Herein, a novel indoxyl-based approach was established for the synthesis of unsymmetrical 3,3′-biindoles from indoles and indoxyls. This approach generated moderate to excellent yields of the desired products (24 examples, up to 98% yield). The present method features broad substrate scope, operational simplicity, high atom economy, and utilization of non-toxic and inexpensive molecular iodine as catalyst. The applicability of this method has been demonstrated by the facile gram-scale synthesis.
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.
Araf51 with improved transglycosylation activities: One engineered biocatalyst for one specific acceptor
Pennec, Aliz,Daniellou, Richard,Loyer, Pascal,Nugier-Chauvin, Caroline,Ferrires, 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.
AZAINDOLE-INDOLE COUPLED DERIVATIVES, PREPARATION METHODS AND USES THEREOF
-
Page/Page column 13, (2010/04/25)
A novel class of azaindole-indole coupled derivatives, their preparation methods, pharmaceutical compositions containing the same and the uses thereof. The common structural feature of these derivatives is that they are coupled by azaindole and indole bi-molecule at different positions, forming extended pi-conjugated systems. Such derivatives inhibited cell growth and proliferation by various mechanisms. The present compounds have improved solubility, increased bioavailability, and thus have enhanced drug actions, and reduced medical dosages and undesired responses.
AZAINDOLE-INDOLE COUPLED DERIVATIVES, PREPARATION METHODS AND USES THEREOF
-
Page/Page column 10, (2010/06/16)
A novel class of azaindole-indole coupled derivatives, their preparation methods, pharmaceutical compositions containing the same and the uses thereof. The common structural feature of these derivatives is that they are coupled by azaindole and indole bi-molecule at different positions, forming extended pi-conjugated systems. Such derivatives inhibited cell growth and proliferation by various mechanisms. The present compounds have improved solubility, increased bioavailability, and thus have enhanced drug actions, and reduced medical dosages and undesired responses.
Synthesis of some cryptolepine analogues, assessment of their antimalarial and cytotoxic activities, and consideration of their antimalarial mode of action
Onyeibor, Onyeka,Croft, Simon L.,Dodson, Hilary I.,Feiz-Haddad, Mohammad,Kendrick, Howard,Millington, Nicola J.,Parapini, Silvia,Phillips, Roger M.,Seville, Scott,Shnyder, Steven D.,Taramelli, Donatella,Wright, Colin W.
, p. 2701 - 2709 (2007/10/03)
A series of analogues of cryptolepine (1) have been synthesized and evaluated for their in vitro antiplasmodial and cytotoxic properties. The IC50 values of several compounds (11a, 11k-m, 11o, 13) against Plasmodium falciparum (strain K1) were 90% at doses of 25 mg kg-1 day -1 with no apparent toxicity to the mice. 2,7-Dibromocryptolepine (15) was evaluated at several dose levels, and a dose-dependent suppression of parasitemia was seen (ED90 = 21.6 mg kg-1 day -1). The antimalarial mode of action of 1 appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation. A number of analogues were assessed for their effects on the inhibition of β-hematin (hemozoin) formation, and the results were compared with their antiplasmodial activities having taken account of their predicted accumulation into the acidic parasite food vacuole. No correlation was seen (r2 = 0.0781) suggesting that the potent antimalarial activity of compounds such as 15 involves other mechanisms in addition to the inhibition of hemozoin formation.
Synthesis and evaluation of analogues of 10H-indolo[3,2-b]-quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase
Guyen, Berangere,Schultes, Christoph M.,Hazel, Pascale,Mann, John,Neidle, Stephen
, p. 981 - 988 (2007/10/03)
We report here the synthesis and evaluation for telomerase-inhibitory and quadruplex DNA binding properties of several rationally-designed quindoline analogues, substituted at the 2- and 7- positions. The ability of these compounds to interact with and stabilise an intramolecular G-quadruplex DNA against increases in temperature was evaluated by a fluorescence-based (FRET) melting assay. The resulting Tm values were found to correlate with their potency for telomerase inhibition, as measured in an in vitro telomerase TRAP assay. The interactions of a number of compounds with a quadruplex DNA molecular structure were simulated by molecular modelling methods. It is concluded that this class of compound represents a new chemical type suitable for further development as telomerase inhibitors.
