Open AccessAnalogues of the Potent Antitumor Compound Leiodermatolide from a Deep-Water Sponge of the Genus Leiodermatium
Author(s) -
Amy E. Wright,
Jill Roberts,
Esther A. Guzmán,
Tara P. Pitts,
Shirley A. Pomponi,
John K. Reed
Publication year - 2017
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/acs.jnatprod.6b01140
Subject(s) - pharmacophore , sponge , stereochemistry , potency , ic50 , genus , chemistry , biological activity , cell culture , biology , in vitro , biochemistry , botany , genetics
Two new analogues of the potent antitumor compound leiodermatolide, which we call leiodermatolides B and C, have been isolated from specimens of a deep-water sponge of the genus Leiodermatium collected off Florida. The compounds were purified using standard chromatographic methods, and the structures defined through interpretation of the HRMS and 1D and 2D NMR data. Leiodermatolide B (2) lacks the C-21 hydroxy group found in leiodermatolide and has equal potency as the parent compound, providing a simpler analogue for possible clinical development. It inhibits the proliferation of the AsPC-1 human pancreatic adenocarcinoma cell line with an IC 50 of 43 nM. Leiodermatolide C (3) has a modified macrolide ring and is over 85-fold less potent with an IC 50 of 3.7 μM against the same cell line. These compounds add to the knowledge of the pharmacophore of this class of potent antitumor agents.