Natural resorcylic acid lactones: A chemical biology approach for anticancer activity

Resorcylic acid lactones (RALs) are fungal polyketides that consist of a β-resorcylic acid residue (2,4-dihydroxybenzoic acid) embedded in a macrolactone ring. RALs exhibit a broad range of biological activities, including anticancer activities. Following discovery of the selective Hsp90 inhibition activity of radicicol, the kinase inhibition activity of hypothemycin, monocillin II, 5Z-7-oxo-zeaenol, and L-783,277 RALs, and the nuclear factor kappa B (NF-κB) inhibition activity of the RAL zearalenone, have attracted great attention as potential therapeutics for cancer treatment. In this minireview, we focus on natural RALs that possess cytotoxic activities [IC₅₀ values < 10 μM (or 4-5 μg/ml)], discussing their structures, isolation, occurrence, biological activities, and anticancer molecular mechanisms.