Synthesis and in vitro bone cell activity of analogues of the cyclohexapeptide dianthin G.
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.
School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1142, New Zealand. m.brimble@auckland.ac.nz.
Zaid
Z
Amso
Renata
R
Kowalczyk
Young-Eun
YE
Park
Maureen
M
Watson
Jian-Ming
JM
Lin
David S
DS
Musson
Jillian
J
Cornish
Margaret A
MA
Brimble
D000368:Aged; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008875:Middle Aged; D015394:Molecular Structure; D010006:Osteoblasts / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D010456:Peptides, Cyclic