2657-28-5Relevant articles and documents
The Mosaic of Rottlerin
Hong, Kenneth K. C.,Ball, Graham E.,Black, David Stc.,Kumar, Naresh
, p. 10668 - 10674 (2015)
The first total synthesis of rottlerin is described. The methodology allows the development of potential novel protein kinase C δ (PKCδ) analogues for better treatment of various diseases. Kamalachalcone A and dimeric rottlerin were synthesized in a very
Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, in Vitro and in Vivo Investigations of Jamunones
Hu, Caijuan,Li, Guoxun,Mu, Yu,Wu, Wenxi,Cao, Bixuan,Wang, Zixuan,Yu, Hainan,Guan, Peipei,Han, Li,Li, Liya,Huang, Xueshi
, p. 6008 - 6020 (2021/05/06)
Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.
Rottlerin: Structure Modifications and KCNQ1/KCNE1 Ion Channel Activity
K?rber, Florian,Lübke, Marco,Le Quoc, Thang,Müller, Jasmin,Matschke, Veronika,Scherkenbeck, Jürgen,Schreiber, Julian A.,Schubert, Janina,Seebohm, Guiscard,Sivanathan, Sivatharushan,Strutz-Seebohm, Nathalie
, (2020/05/25)
The slow delayed rectifier potassium current (IKs) is formed by the KCNQ1 (Kv7.1) channel, an ion channel of four α-subunits that modulates KCNE1 β-subunits. IKs is central to the repolarization of the cardiac action potential. Loss of function mutation reducing ventricular cardiac IKs cause the long-QT syndrome (LQTS), a disorder that predisposes patients to arrhythmia and sudden death. Current therapy for LQTS is inadequate. Rottlerin, a natural product of the kamala tree, activates IKs and has the potential to provide a new strategy for rational drug therapy. In this study, we show that simple modifications such as penta-acetylation or penta-methylation of rottlerin blunts activation activity. Total synthesis was used to prepare side-chain-modified derivatives that slowed down KCNQ1/KCNE1 channel deactivation to different degrees. A binding hypothesis of rottlerin is provided that opens the way to improved IKs activators as novel therapeutics for the treatment of LQTS.
