Trichodestruxins A-D: Cytotoxic Cyclodepsipeptides from the Endophytic Fungus Trichoderma harzianum

  • J Nat Prod. 2020 Dec 24;83(12):3635-3641. doi: 10.1021/acs.jnatprod.0c00808.
Zhiguo Liu  1 ,  Yi Sun  1 ,  Mengyue Tang  1  2 ,  Peng Sun  1 ,  Anqi Wang  1 ,  Yanqi Hao  1 ,  Yanan Wang  3 ,  Yuehu Pei  2
Affiliations
  • 1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China.
  • 2. School of Pharmacy, Harbin Medical University, Harbin 150081, People's Republic of China.
  • 3. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
PMID: 33301677 DOI: 10.1021/acs.jnatprod.0c00808
Abstract

Four new cyclodepsipeptides, trichodestruxins A-D (1-4), together with destruxin E2 chlorohydrin (5) and destruxin A2 (6), were isolated from the plant endophytic fungus Trichoderma harzianum by a bioassay-guided fractionation method. Their planar structures were elucidated on the basis of 1D and 2D NMR and MS/MS spectroscopic analyses. The stereochemical configuration was established by application of the advanced Marfey's method, J-based configuration analysis, Mosher's method, and chemical derivatizations. Trichodestruxin B contains hydroxy acid fragments of the THPA unit, while trichodestruxins A and C contain the β-methylproline moiety. All cyclodepsipeptides displayed cytotoxicity against HT-29, A549, and/or P388 cell lines with IC50 values of 0.7-19.1 μM.