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Synthesis of 21‐Alkylidenes and 21‐Alkylol Analogues of Uscharin and Their Effects on Intracellular Calcium in Cardiac Cells
Author(s) -
Zhou Xiaobo,
Chen Li,
Jiang ZhiHong,
Chen Xiaoyi,
Luo Pei,
Bai LiPing
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201900108
Subject(s) - calcium in biology , cytotoxicity , contractility , intracellular , calcium , chemistry , moiety , inotrope , contraction (grammar) , cardiac muscle , myocyte , biophysics , medicine , stereochemistry , biochemistry , biology , in vitro , organic chemistry
Five 21‐alkylidenes ( 2 ‐ 6 ) and a 21‐alkylol ( 7 ) derivatives of uscharin ( 1 ) were synthesized by aldol condensation reaction and aldol reaction of uscharin with aromatic aldehydes, respectively. We investigated the ability of uscharin and its derivatives to interfere with the intracellular calcium level by flow cytometry and contractile characteristics at the single cell level by time‐lapse microscopy in H9c2 cells. Changes of spontaneous calcium oscillations in beating HL‐1 cells were also studied by a high‐throughput Fluorometric Imaging Plate Reader (FLIPR) assay. We reported for the first time that uscharin could produce increased contraction strength in cardiac muscle cells while it showed a significant cytotoxicity to atrial cells. Unlike uscharin, 6 induced a marked increase of myocardial contractility, whereas 6 neither caused irregular frequency of oscillations nor cardiac cytotoxic effects under tested conditions. Structural modification on the butenolide moiety of uscharin showed a reduction of cardiac cytotoxicity and exhibited potential for use as an inotropic agent for the treatment of heart failure.