943-88-4Relevant articles and documents
8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
Xing, Gang,Zhi, Zhengxing,Yi, Ce,Zou, Jitian,Jing, Xuefeng,Yiu-Ho Woo, Anthony,Lin, Bin,Pan, Li,Zhang, Yuyang,Cheng, Maosheng
, (2021/07/19)
β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.
Design, synthesis, and molecular docking study of novel quinoline-based bis-chalcones as potential antitumor agents
Insuasty, Daniel,García, Stephanie,Abonia, Rodrigo,Insuasty, Braulio,Quiroga, Jairo,Nogueras, Manuel,Cobo, Justo,Borosky, Gabriela L.,Laali, Kenneth K.
, (2021/06/01)
A novel series of quinoline-based symmetrical and unsymmetrical bis-chalcones was synthesized via a Claisen–Schmidt condensation reaction between 3-formyl-quinoline/quinolone derivatives with acetone or arylidene acetones, respectively, by using KOH/MeOH/H2O as a reaction medium. Twelve of the obtained compounds were evaluated for their in vitro cytotoxic activity against 60 different human cancer cell lines according to the National Cancer Institute protocol. Among the screened compounds, the symmetrical N-butyl bis-quinolinyl-chalcone 14g and the unsymmetrical quinolinyl-bis-chalcone 17o bearing a 7-chloro-substitution on the N-benzylquinoline moiety and 4-hydroxy-3-methoxy substituent on the phenyl ring, respectively, exhibited the highest overall cytotoxicity against the evaluated cell lines with a GI50 range of 0.16–5.45 μM, with HCT-116 (GI50 = 0.16) and HT29 (GI50 = 0.42 μM) (colon cancer) representing best-case scenarios. Notably, several GI50 values for these compounds were lower than those of the reference drugs doxorubicin and 5-FU. Docking studies performed on selected derivatives yielded very good binding energies in the active site of proteins that participate in key carcinogenic pathways.
Inhibition of Autophagy by a Small Molecule through Covalent Modification of the LC3 Protein
Chen, Kaixian,Chen, Zhifeng,Dang, Yongjun,Ding, Hong,Fan, Shijie,Hu, Junchi,Jiang, Hualiang,Li, Lianchun,Li, Quanfu,Lin, Tingting,Lu, Junyan,Luo, Cheng,Otomo, Chinatsu,Otomo, Takanori,Tan, Minjia,Tao, Hongru,Wan, Wei,Wen, Yi,Xie, Yuli,Xu, Pan,Yao, Zhiyi,Yue, Liyan,Zhang, Bidong,Zhang, Naixia,Zhang, Yuanyuan,Zhou, Bing,Zhu, Mingrui
supporting information, p. 26105 - 26114 (2021/11/09)
The autophagic ubiquitin-like protein LC3 functions through interactions with LC3-interaction regions (LIRs) of other autophagy proteins, including autophagy receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention of autophagy. Post-translational modifications like acetylation of Lys49 on the LIR-interacting surface could disrupt the interaction, offering an opportunity to design covalent small molecules interfering with the interface. Through screening covalent compounds, we discovered a small molecule modulator of LC3A/B that covalently modifies LC3A/B protein at Lys49. Activity-based protein profiling (ABPP) based evaluations reveal that a derivative molecule DC-LC3in-D5 exhibits a potent covalent reactivity and selectivity to LC3A/B in HeLa cells. DC-LC3in-D5 compromises LC3B lipidation in vitro and in HeLa cells, leading to deficiency in the formation of autophagic structures and autophagic substrate degradation. DC-LC3in-D5 could serve as a powerful tool for autophagy research as well as for therapeutic interventions.
