Ionization, lipophilicity, and molecular modeling to investigate permeability and other biological properties of amlodipine.
This paper uses a recent approach toward drug discovery, in which in silico tools and experimental data are combined together to study the structural features of amlodipine and their relevance in the peculiar pharmacodynamic and pharmacokinetic profiles of this long acting calcium antagonist. Results reveal for amlodipine two families of conformers (folded and extended) but also demonstrate that protonation is the predominant factor governing amlodipine intermolecular interactions among which ionic forces play a major role.
Caron
Giulia
G
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, I-10125 Torino, Italy. giulia.caron@unito.it
Ermondi
Giuseppe
G
Damiano
Alessandro
A
Novaroli
Laura
L
Tsinman
Oksana
O
Ruell
Jeffrey A
JA
Avdeef
Alex
A
D017311:Amlodipine / Q000737:chemistry*; D002121:Calcium Channel Blockers / Q000737:chemistry*; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions; D008567:Membranes, Artificial; D008958:Models, Molecular; D008968:Molecular Conformation; D010539:Permeability; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D007477:Ions; D008567:Membranes, Artificial; D017311:Amlodipine