Synthesis and preliminary biological evaluation of truncated zoanthenol analogues.
Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique structural element. In this report, we designed and synthesized ABC-ring 6 and CDEFG-ring 7, which are truncated analogues of the northern and southern hemispheres of zoanthenol 5, respectively, and which incorporate all of the functionality of each hemisphere. A preliminary SAR study suggested that the hydrochloride of the CEFG-ring portion is an active pharmacophore for suppressing the growth of interleukin-6-dependent MH60 cells.
Hirai
Go
G
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
Oguri
Hiroki
H
Hayashi
Masahiko
M
Koyama
Koji
K
Koizumi
Yuuki
Y
Moharram
Sameh M
SM
Hirama
Masahiro
M
D000470:Alkaloids / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003063:Cnidaria / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006572:Heterocyclic Compounds, Bridged-Ring / Q000138:chemical synthesis / Q000494:pharmacology*; D006825:Hybridomas; D051379:Mice; D018716:Molecular Mimicry; D010024:Osteoporosis / Q000188:drug therapy; D013329:Structure-Activity Relationship; D000093242:Interleukin-6 Inhibitors
D000470:Alkaloids; D006572:Heterocyclic Compounds, Bridged-Ring; D000093242:Interleukin-6 Inhibitors; C457061:zoanthenol