Search for Hsp90 inhibitors with potential anticancer activity: isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran desert.

In an effort to discover small molecule inhibitors of Hsp90, we have screened over 500 EtOAc extracts of Sonoran desert plant-associated fungi using a two-stage strategy consisting of a primary cell-based heat shock induction assay (HSIA) followed by a secondary biochemical luciferase refolding assay (LRA). Bioassay-guided fractionation of extracts active in these assays derived from Chaetomium chiversii and Paraphaeosphaeria quadriseptata furnished the Hsp90 inhibitors radicicol (1) and monocillin I (2), respectively. In SAR studies, 1, 2, and their analogues, 3-16, were evaluated in these assays, and the antiproliferative activity of compounds active in both assays was determined using the breast cancer cell line MCF-7.

Cytotoxic and other metabolites of Aspergillus inhabiting the rhizosphere of Sonoran desert plants.

In a study to discover potential anticancer agents from rhizosphere fungi of Sonoran desert plants cytotoxic EtOAc extracts of four Aspergillus strains have been investigated. Two new metabolites, terrequinone A (1) and terrefuranone (2), along with Na-acetyl aszonalemin (LL-S490beta) (3) were isolated from As. terreus occurring in the rhizosphere of Ambrosia ambrosoides, whereas As.