Structure Modification of FXR Antagonistic Chalcones and Their Inhibitory Effects on NSCLC Cell Proliferation and Metastasis. (11th April 2022)

• Record Type: Journal Article
• Authors: Niu, Shuaishuai; Zhang, Guoning; Wang, Na; Lv, Guangyao; Liu, Jinsong; Wang, Hongbo; Fang, Wei‐Shuo
• Is Part Of: ChemMedChem. Volume 17:Number 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-11
• Subjects: chalcone -- FXR antagonist -- Antiproliferation -- NSCLC; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100778
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Although the farnesoid X receptor (FXR) has been regarded as a promising drug target for metabolic diseases as well as anti‐inflammatory, antitumor and antiviral actions, the antagonism by FXR ligands are still underrepresented in current FXR targeted therapies. In this study, we discovered selective FXR antagonists through structure optimization from the polyoxygenated chalcone scaffold. The selective antagonist 6 p [2‐methoxy‐2'‐hydroxy‐4'‐(4''‐methoxy‐4''‐oxo‐ E ‐crotonyl) chalcone] is not only inhibitory toward non‐small‐cell lung cancer (NSCLC) cell proliferation in an FXR‐dependent manner, but is also active in metastasis models. Taken together, this chalcone‐based FXR antagonist has the potential for the targeted therapy of NSCLC in which FXR is highly expressed. Abstract : A chalcone derivative 6 p was synthesized and identified as an FXR‐selective antagonist, which inhibits non‐small‐cell lung cancer (NSCLC) cell proliferation and migration in an FXR‐dependent manner. It blocks cell cycle in G1 phase and promotes apoptosis. These results demonstrate the potential of this type of FXR antagonist as targeted therapeutics for NSCLC.