2. Academic Validation
  3. Cytotoxic Trichothecene Macrolides Produced by the Endophytic Myrothecium roridum

Cytotoxic Trichothecene Macrolides Produced by the Endophytic Myrothecium roridum

  • J Nat Prod. 2019 Jun 28;82(6):1503-1509. doi: 10.1021/acs.jnatprod.8b01034.
Li Shen 1 2 3 4,  Chun-Zhi Ai 5,  Yong-Chun Song 3,  Feng-Wu Wang 3,  Rui-Hua Jiao 3,  Ai-Hua Zhang 3,  Hui-Zi Man 6,  Ren-Xiang Tan 3
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Medical College , Yangzhou University , Yangzhou 225001 , People's Republic of China.
  • 2 Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases , Yangzhou University , Yangzhou 225001 , People's Republic of China.
  • 3 Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology , Nanjing University , Nanjing 210093 , People's Republic of China.
  • 4 Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine , Yangzhou University , Yangzhou 225009 , People's Republic of China.
  • 5 Institute for Advanced Study, Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering , Shenzhen University , Shenzhen 518061 , People's Republic of China.
  • 6 Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics , Chinese Academy of Sciences , Dalian 116023 , People's Republic of China.
PMID: 31117520 DOI: 10.1021/acs.jnatprod.8b01034
Abstract

Six new macrolides named myrothecines D-G (1-4), 16-hydroxymytoxin B (5), and 14'-dehydrovertisporin (6), including four 10,13-cyclotrichothecane derivatives, in addition to 12 known compounds (7-18), were isolated from three endophytic Myrothecium roridum, IFB-E008, IFB-E009, and IFB-E012. The isolated compounds were characterized by MS, NMR, CD, and single-crystal X-ray crystallography. The isolated macrolides exhibited an antiproliferation effect against chronic myeloid leukemia K562 and colorectal carcinoma SW1116 cell lines. Compounds 1-6 were cytotoxic, with IC50 values ranging between 56 nM and 16 μM. Since slight structural changes led to obvious activity differences, the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were then used to explore the 3D QSAR (three-dimensional quantitative structure-activity relationship) of these macrolides. The result showed that the steric, electrostatic, hydrophobic, and H-bond acceptor factors were involved in their cytotoxicity and provided an in-depth understanding of the structure-activity relationships of these metabolites.

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