Borrelidins F-I, cytotoxic and cell migration inhibiting agents from mangrove-derived Streptomyces rochei SCSIO ZJ89

Bioorg Med Chem. 2018 May 1;26(8):1488-1494. doi: 10.1016/j.bmc.2018.01.010. Epub 2018 Feb 7.

Abstract

Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from Streptomyces rochei SCSIO ZJ89 originating from a mangrove-derived sediment sample. These structurally diverse metabolites enabled a number of new structure-activity relationships (SARs) to be identified, especially with respect to the different configurations at the C11-OH and C12-C15 double bonds for which the absolute configurations were determined using spectroscopic methods. Importantly, borrelidin H (4) was found to have a therapeutic window superior to that of borrelidin A (1) in vitro and could inhibit migration of cancer cells.

Keywords: Borrelidin; Cancer; Cytotoxic activity; Migration; Streptomyces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / isolation & purification
  • Fatty Alcohols / pharmacology
  • Humans
  • Molecular Structure
  • Streptomyces / chemistry*
  • Structure-Activity Relationship
  • Wound Healing / drug effects

Substances

  • Antineoplastic Agents
  • Fatty Alcohols
  • borrelidin