Resorcylic acid lactones with cytotoxic and NF-κB inhibitory activities and their structure-activity relationships.
J Nat Prod
; 74(5): 1126-31, 2011 May 27.
Article
in En
| MEDLINE
| ID: mdl-21513293
ABSTRACT
As part of our ongoing investigation of filamentous fungi for anticancer leads, an active fungal extract was identified from the Mycosynthetix library (MSX 63935; related to Phoma sp.). The initial extract exhibited cytotoxic activity against the H460 (human non-small cell lung carcinoma) and SF268 (human astrocytoma) cell lines and was selected for further study. Bioactivity-directed fractionation yielded resorcylic acid lactones (RALs) 1 (a new natural product) and 3 (a new compound) and the known RALs zeaenol (2), (5E)-7-oxozeaenol (4), (5Z)-7-oxozeaenol (5), and LL-Z1640-1 (6). Reduction of (5E)-7-oxozeaenol (4) with sodium borohydride produced 3, which allowed assignment of the absolute configuration of 3. Other known resorcylic acid lactones (7-12) were purchased and assayed in parallel for cytotoxicity with isolated 1-6 to investigate structure-activity relationships in the series. Moreover, the isolated compounds (1-6) were examined for activity in a suite of biological assays, including antibacterial, mitochondria transmembrane potential, and NF-κB. In the latter assay, compounds 1 and 5 displayed sub-micromolar activities that were on par with the positive control, and as such, these compounds may serve as a lead scaffold for future medicinal chemistry studies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zearalenone
/
NF-kappa B
/
Lactones
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Nat Prod
Year:
2011
Document type:
Article
Affiliation country:
United States