Design, synthesis, and biological activities of madindoline analogues.
A research program is under way to develop a series of madindoline-based inhibitors targeting interleukin 6. Such inhibitors will have potential use in fighting a variety of diseases for which no effective therapeutic drugs currently exist. Madindoline is no longer available from natural sources. Consequently, we have developed a purely synthetic route to ensure a supply of the compound. The synthesis of a range of analogues is described, all of which were evaluated for their inhibitory activity against the growth of IL-6-dependent 7TDI cells. From these assays, several synthetic madindoline analogues were identified as highly promising candidates for further development.
The Kitasato Institute, and Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, School of Pharmaceutical Sciences, Kitasato University, Japan.
Daisuke
D
Yamamoto
Toshiaki
T
Sunazuka
Tomoyasu
T
Hirose
Naoto
N
Kojima
Eisuke
E
Kaji
Satoshi
S
Omura
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; C103158:madindoline A