Isolation and Structure Elucidation of Cytotoxic Saccharothriolides D to F from a Rare Actinomycete Saccharothrix sp. and Their Structure-Activity Relationship

  • J Nat Prod. 2016 Jul 22;79(7):1891-5. doi: 10.1021/acs.jnatprod.6b00372.
Shan Lu  1 ,  Shinichi Nishimura  1 ,  Masashi Ito  2 ,  Toshio Tsuchida  2 ,  Hideaki Kakeya  1
Affiliations
  • 1. Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
  • 2. Bioresource Laboratories, MicroBioPharm Japan Co., Ltd. (MBJ) , Iwata, Shizuoka 438-0078, Japan.
PMID: 27332142 DOI: 10.1021/acs.jnatprod.6b00372
Abstract

Three new 10-membered macrolides, saccharothriolides D-F (1-3), were isolated from a rare actinomycete, Saccharothrix sp. A1506. The planar structures were determined from analysis of extensive NMR and HR-ESI-MS data, and the absolute configurations were established by ECD spectroscopy analysis. Saccharothriolides D (1) and E (2) were determined to be C-2 epimers of saccharothriolides A (4) and B (5), respectively. Saccharothriolide F (3) was identified to be a demethylated congener of saccharothriolides D (1) and A (4) at the C-2 position. The availability of compounds 1-6 enabled a structure-activity relationship study that revealed the importance of the phenolic hydroxy group at C-2″ and the stereochemistry of C-2 for the inhibition of human fibrosarcoma HT1080 cell growth.