- Synthesis, conformation, and biological activity of teleocidin mimics, benzolactams. A clarification of the conformational flexibility problem in structure-activity studies of teleocidins
-
Tumor-promoter teleocidins and their active congeners (indolactams) are known to exist in an equilibrium between at least two conformational states in solution, the twist and sofa form, due to cis-trans isomerization of the amide bond and the steric effects of substituents on the nine-membered lactam ring. Benzolactam-Vs, in which the indole ring of indolactams is replaced with a benzene ring, were designed and synthesized in an attempt to reproduce the active conformation of teleocidins. Among these benzolactams, eight-membered lactams (benzolactam-V8) can only exist in the twist form, and 9- and 10-membered lactams (benzolactam-V9 and -V10) exist exclusively in the sofa form in solution. The stronger biological activity of benzolactam-V-8-310 than that of indolactam-V (IL-V) and the inactivity of benzolactam-V-9-310 for differentiation inducing activity of HL-60 clearly indicated that the twist form is close to the active conformation of teleocidins.
- Endo, Yasuyuki,Ohno, Michihiro,Hirano, Masaaki,Itai, Akiko,Shudo, Koichi
-
p. 1841 - 1855
(2007/10/03)
-
- Designed Molecules Reproducing the Two Conformations of Teleocidins.
-
Tumor-promoting teleocidins are known to exist in an equilibrium between two conformational states, the twist form and sofa form, in solution.Benzolactam-Vs, in which the indole ring of indolactams was replaced with a benzene ring, were designed in an att
- Ohno, Michihiro,Endo, Yasuyuki,Hirano, Masaaki,Itai, Akiko,Shudo, Koichi
-
p. 8119 - 8122
(2007/10/02)
-