Cyclizidine-Type Alkaloids from Streptomyces sp. HNA39

J Nat Prod. 2018 Feb 23;81(2):394-399. doi: 10.1021/acs.jnatprod.7b01055. Epub 2018 Feb 1.

Abstract

Eight new cyclizidine-type alkaloids (1-8) and one known alkaloid (9) were identified from the chemical investigations of a marine-derived actinomycete, Streptomyces sp. HNA39. Among these alkaloids, compounds 3, 7, and 8 contain a chlorine atom, and the known alkaloid, (+)-ent-cyclizidine (9), is now first reported as a natural product. Their structures were elucidated by extensive NMR-spectroscopic analysis and HRESIMS data. The absolute configurations of all of the compounds were established by ECD calculations. Cytotoxicity evaluations of all of the compounds showed that compound 2 exhibited significant activity against the PC3 and HCT116 human-cancer-cell lines with IC50 values of 0.52 ± 0.03 and 8.3 ± 0.1 μM, respectively. Interestingly, compounds 2, 5, 7, and 8 exhibited moderate inhibition against the ROCK2 protein kinase with IC50 values from 7.0 ± 0.8 to 42 ± 3 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacology
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Cell Line, Tumor
  • Chlorine / chemistry
  • Chlorine / pharmacology
  • Cytotoxins / chemistry
  • Cytotoxins / pharmacology
  • HCT116 Cells
  • Humans
  • Indolizidines / chemistry*
  • Indolizidines / pharmacology
  • Magnetic Resonance Spectroscopy / methods
  • PC-3 Cells
  • Streptomyces / chemistry*
  • rho-Associated Kinases / antagonists & inhibitors

Substances

  • Alkaloids
  • Biological Products
  • Cytotoxins
  • Indolizidines
  • ent-cyclizidine
  • Chlorine
  • rho-Associated Kinases