Ascomylactams A-C, Cytotoxic 12- or 13-Membered-Ring Macrocyclic Alkaloids Isolated from the Mangrove Endophytic Fungus Didymella sp. CYSK-4, and Structure Revisions of Phomapyrrolidones A and C

  • J Nat Prod. 2019 Jul 26;82(7):1752-1758. doi: 10.1021/acs.jnatprod.8b00918.
Yan Chen  1  2 ,  Zhaoming Liu  1  3 ,  Yun Huang  4  5 ,  Lan Liu  2 ,  Jianguo He  2 ,  Lan Wang  5 ,  Jie Yuan  4 ,  Zhigang She  1  2
Affiliations
  • 1. School of Chemistry , Sun Yat-sen University , Guangzhou 510275 , People's Republic of China.
  • 2. School of Marine Sciences, Sun Yat-sen University , South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center , Guangzhou 510006 , People's Republic of China.
  • 3. Guangdong Institute of Microbiology , Guangzhou 510075 , People's Republic of China.
  • 4. Department of Biochemistry, Zhongshan School of Medicine , Sun Yat-sen University , Guangzhou 510080 , People's Republic of China.
  • 5. Department of Pathogen Biology and Immunology, School of Basic Courses , Guangdong Pharmaceutical University , Guangzhou 510006 , People's Republic of China.
PMID: 31251621 DOI: 10.1021/acs.jnatprod.8b00918
Abstract

Three new 12- or 13-membered-ring macrocyclic Alkaloids, named ascomylactams A-C (1-3), along with the analogues phomapyrrolidone C (4) and phomapyrrolidone A (5) were isolated from the mangrove endophytic fungus Didymella sp. CYSK-4. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. The structures and absolute configurations of 1 and 2 were determined by single-crystal X-ray diffraction experiments, which represents the first crystal structures described for a (6/5/6/5) tetracyclic skeleton fused with a 12- or 13-membered-ring macrocyclic moiety. The configurations of phomapyrrolidone C (4) and phomapyrrolidone A (5) were revised by detailed analysis of the NMR data. In a cytotoxic assay, compounds 1 and 3 showed moderate cytotoxicity against MDA-MB-435, MDA-MB-231, SNB19, HCT116, NCI-H460, and PC-3 human Cancer cell lines, with IC50 values in the range of 4.2-7.8 μM.