Natural resorcylic acid lactones: A chemical biology approach for anticancer activity
Shilpa Kuttikrishnan, Kirti S. Prabhu, Ahmed H. Al Sharie, Yazan O. Al Zu’bi, Feras Q. Alali, Nicholas H. Oberlies, Aamir Ahmad, Tamam El‐Elimat, Shahab Uddin
Abstract
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.