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Caulerpenyne and Related Bis‐enol Esters Are Novel‐Type Inhibitors of Human 5‐Lipoxygenase
Author(s) -
Richter Phillipp,
Schubert Gregor,
Schaible Anja Maria,
Cavas Levent,
Werz Oliver,
Pohnert Georg
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402065
Subject(s) - lipoxygenase , arachidonate 5 lipoxygenase , chemistry , sesquiterpene , stereochemistry , inhibitory postsynaptic potential , biochemistry , enol , structure–activity relationship , enzyme , biology , in vitro , arachidonic acid , neuroscience , catalysis
Caulerpenyne (CYN) is a sesquiterpene from green algae with known inhibitory properties against soybean lipoxygenase. Here we introduce a detailed structure–activity study elucidating the inhibitory effects of CYN and a library of six synthetic CYN analogues on isolated human 5‐lipoxygenase (5‐LO) and cellular 5‐LO in polymorphonuclear leukocytes. Essential structural elements are identified and a structurally simplified inhibitor is introduced. The modes of 5‐LO inhibition by CYN and the synthetic inhibitors cannot be assigned to any of the known categories of lipoxygenase inhibitors. These compounds clearly interfere directly with 5‐LO and represent rather small and flexible molecules, with unique structures among 5‐LO inhibitors identified thus far.