Synthesis and in Vitro Bone Cell Activity of Analogues of the Cyclohexapeptide Dianthin G

Org Biomol Chem. 2016 Jul 14;14(26):6231-43. doi: 10.1039/c6ob00983b. Epub 2016 Jun 6.

Abstract

The cyclohexapeptide natural product dianthin G promotes osteoblast (bone-forming cell) proliferation in vitro at nanomolar concentrations, and is therefore considered a promising candidate for the treatment of osteoporosis. An N(α)-methyl amide bond scan of dianthin G was performed to probe the effect of modifying amide bonds on osteoblast proliferation. In addition, to provide greater structural diversity, a series of dicarba dianthin G analogues was synthesised using ring closing metathesis. Dianthin G and one novel dicarba analogue increased the number of human osteoblasts and importantly they did not increase osteoclast (bone-resorbing cell) differentiation in bone marrow cells.

MeSH terms

  • Aged
  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Mice
  • Middle Aged
  • Molecular Structure
  • Osteoblasts / drug effects*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Structure-Activity Relationship

Substances

  • Peptides, Cyclic