Herbicidins from Streptomyces sp. CB01388 Showing Anti- Cryptosporidium Activity

  • J Nat Prod. 2018 Apr 27;81(4):791-797. doi: 10.1021/acs.jnatprod.7b00850.
Jian-Jun Chen  1 ,  Mostafa E Rateb  1 ,  Melissa S Love  2 ,  Zhengren Xu  1 ,  Dong Yang  1  3 ,  Xiangcheng Zhu  4  5 ,  Yong Huang  4 ,  Li-Xing Zhao  6 ,  Yi Jiang  6 ,  Yanwen Duan  4  5 ,  Case W McNamara  2 ,  Ben Shen  1  3  7
Affiliations
  • 1. Department of Chemistry , The Scripps Research Institute , Jupiter , Florida 33458 , United States.
  • 2. California Institute for Biomedical Research , La Jolla , California 92037 , United States.
  • 3. Natural Products Library Initiative at The Scripps Research Institute , The Scripps Research Institute , Jupiter , Florida 33458 , United States.
  • 4. Xiangya International Academy of Translational Medicine , Central South University , Changsha , Hunan 410013 , People's Republic of China.
  • 5. Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery , Changsha , Hunan 410013 , People's Republic of China.
  • 6. Yunnan Institute of Microbiology , Yunnan University , Kunming , Yunnan 650091 , People's Republic of China.
  • 7. Department of Molecular Medicine , The Scripps Research Institute , Jupiter , Florida 33458 , United States.
PMID: 29469575 DOI: 10.1021/acs.jnatprod.7b00850
Abstract

A high-content imaging assay was used to screen the fraction collection of the Natural Product Library at The Scripps Research Institute for inhibitors of Cryptosporidium parvum. A chemical investigation of one strain, Streptomyces sp. CB01388, resulted in the isolation of six herbicidins (1-6), one of which is new (herbicidin L, 1). Five of the six herbicidins (1-3, 5, 6) showed moderate inhibitory activity against C. parvum, with 1 and 6 comparable to the FDA-approved drug nitazoxanide, and 2-6 showed no toxicity to the host HCT-8 cells and human HEK293T and HepG2 cells. These findings highlight the herbicidin scaffold for anti- Cryptosporidium drug development.