Two Highly Populated Conformations at Room Temperature of Monterine and Granjine, Antitumor Bisbenzylisoquinoline Alkaloids: Origin and Tridimensional Structures.
Monterine 1 as well as granjine 3, 1R,1'S configured biphenylic bisbenzylisoquinoline alkaloids, generate two highly populated conformers. The interconversion of two forms was detected by saturation tranfer in (1)H NMR NOEs experiments. Tridimensional structure of the conformers was determined on the basis of (1)H NMR analysis of anisotropic shielding protons, by NOEs measurements and vicinal proton coupling constants of CH1-CH(2)alpha and CH1'-CH(2)alpha'. The structures established from NMR data were further refined to observe the mobility of 3D conformations by molecular dynamics simulation in vacuo. The highly populated conformers, monterine 1a and 1b, as well as granjine 3a and 3b, are interconvertible by rotation about the C1'-Calpha', Calpha'-C9', and C11'-C11 bonds and inversion of the benzyl D ring by reference to CH(2)alpha'. The slow exchange system was investigated by dynamic NMR spectroscopy: DeltaG()(c) 77.9 KJ/mol and k(c) 200 s(-)(1) for monterine 1; DeltaG()(c) 77.7 KJ/mol and k(c) 211 s(-)(1) for granjine 3. Natural and synthetic biphenylic bisbenzylisoquinolines displayed, in vitro, cytotoxic activities against human prostate and breast cancer cell lines.
Jossang
Akino
A
Laboratoire de Chimie, CNRS URA 401, Muséum National d'Histoire Naturelle, 63 rue Buffon 75005 Paris, France; Centre de Biochimie Structurale, CNRS UMR C9955, INSERM U414, Université Montpellier I, 34060 Montpellier, France; Departamento de Quimica, Universidad de Antioquia, AA 1226 Medellin, Colombia; Laboratoire de Pharmacie Clinique et de Biotechnique (GREPO), UFR de Pharmacie de Grenoble, 38700 La Tronche, France; and Laboratoire de Pharmacognosie, CNRS URA 1843, Faculté de Pharmacie, Université de Paris XI, 92296 Châtenay-Malabry Cedex, France.
Cavé
Adrien
A
Saez
Jairo
J
Bartoli
Marie Hélène
MH
Cavé
André
A
Jossang
Per
P