99985-06-5Relevant articles and documents
Structure-Activity Relationship in the Leucettine Family of Kinase Inhibitors
Tahtouh, Tania,Durieu, Emilie,Villiers, Beno?t,Bruyère, Céline,Nguyen, Thu Lan,Fant, Xavier,Ahn, Kwang H.,Khurana, Leepakshi,Deau, Emmanuel,Lindberg, Mattias F.,Sévère, Elodie,Miege, Frédéric,Roche, Didier,Limanton, Emmanuelle,L’Helgoual’ch, Jean-Martial,Burgy, Guillaume,Guiheneuf, Solène,Herault, Yann,Kendall, Debra A.,Carreaux, Fran?ois,Bazureau, Jean-Pierre,Meijer, Laurent
supporting information, p. 1396 - 1417 (2022/01/03)
The protein kinase DYRK1A is involved in Alzheimer's disease, Down syndrome, diabetes, viral infections, and leukemia. Leucettines, a family of 2-aminoimidazolin-4-ones derived from the marine sponge alkaloid Leucettamine B, have been developed as pharmacological inhibitors of DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases). We report here on the synthesis and structure-activity relationship (SAR) of 68 Leucettines. Leucettines were tested on 11 purified kinases and in 5 cellular assays: (1) CLK1 pre-mRNA splicing, (2) Threonine-212-Tau phosphorylation, (3) glutamate-induced cell death, (4) autophagy and (5) antagonism of ligand-activated cannabinoid receptor CB1. The Leucettine SAR observed for DYRK1A is essentially identical for CLK1, CLK4, DYRK1B, and DYRK2. DYRK3 and CLK3 are less sensitive to Leucettines. In contrast, the cellular SAR highlights correlations between inhibition of specific kinase targets and some but not all cellular effects. Leucettines deserve further development as potential therapeutics against various diseases on the basis of their molecular targets and cellular effects.
Benzylidene-linked thiohydantoin derivatives as inhibitors of tyrosinase and melanogenesis: Importance of the β-phenyl-α,β-unsaturated carbonyl functionality
Kim, Hye Rim,Lee, Hye Jin,Choi, Yeon Ja,Park, Yun Jung,Woo, Youngwoo,Kim, Seong Jin,Park, Min Hi,Lee, Hee Won,Chun, Pusoon,Chung, Hae Young,Moon, Hyung Ryong
, p. 1410 - 1417 (2014/10/15)
Based on the structural characteristics of the heterocyclic scaffolds of substituted benzylidene-hydantoin, -pyrrolidinedione, and -thiazolidinedione derivatives with potent tyrosinase inhibitory activity, substituted benzylidene derivatives with a 2-thio
Benzylidene 2-aminoimidazolones derivatives: Synthesis and in vitro evaluation of anti-tumor carcinoma activity
Ling, Yong,Wang, Zhi-Qiang,Xiao, You-An,Zhu, Chenyu,Shen, Liucen,Wang, Xue-Min,Hui, Yi,Wang, Xin-Yang
, p. 1081 - 1084 (2013/11/19)
A series of benzylidene 2-aminoimidazolones derivatives were synthesized. Most compounds displayed strong inhibitory activity on the proliferation of human HepG2 cells in vitro. The active compounds were further evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against five human cancer cell lines in vitro. Compound 2b exhibited the strongest antitumor activities with IC50 values ranging from 12.87-17.10 μM which were nearly 1-3.5 fold less than that of 5-FU (IC50=18.39-56.12 μM) in vitro. Furthermore, compound 2b could induce SMMC-7721 cell apoptosis in a dose-dependent manner. Therefore, our novel findings may provide a new framework for the design of new benzylidene 2-aminoimidazolones derivatives for the treatment of cancer.
