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The Calcium‐Chelating Capability of Tetrahydrofuranic Moieties Modulates the Cytotoxicity of Annonaceous Acetogenins
Author(s) -
Liaw ChihChuang,
Liao WenYing,
Chen ChienSheng,
Jao ShuChuan,
Wu YangChang,
Shen ChiaNing,
Wu ShihHsiung
Publication year - 2011
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201100717
Subject(s) - isothermal titration calorimetry , chelation , calcium , chemistry , intracellular , biophysics , calcium in biology , cytotoxicity , titration , membrane , depolarization , nuclear magnetic resonance spectroscopy , stereochemistry , biochemistry , inorganic chemistry , biology , organic chemistry , in vitro
Forced entry : NMR spectroscopy and isothermal titration calorimetry show that calcium ions are chelated by the hydroxylated THF ring of acetogenins, which results in formation of complexes that aid the Ca 2+ cations in penetrating cell membranes and in elevating the intracellular calcium level (see picture). This disruption of intracellular calcium homeostasis induces mitochondrial depolarization and mediates cell toxicity.