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

Drug Discov Today. 2022 Feb;27(2):547-557. doi: 10.1016/j.drudis.2021.10.001. Epub 2021 Oct 13.


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.

Keywords: 5Z-7-oxo-zeaenol; Heat shock protein 90 inhibitors; Hypothemycin; Protein kinase inhibitors; Radicicol; Resorcylic acid lactones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biology
  • Lactones* / chemistry
  • Lactones* / pharmacology
  • Molecular Structure
  • NF-kappa B*


  • Lactones
  • NF-kappa B