Combined 3D QSAR and molecular docking studies to reveal novel cannabinoid ligands with optimum binding activity.
The combination of NMR spectroscopy and molecular modeling studies provided the putative bioactive conformation for the analgesic cannabinoid (CB) ligand (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethylhydroxy-6H-dibenzo[b,d]pyranyl)-2-hexyl 1,3-dithiolane which served as a template in reported three-dimensional quantitative structure-activity relationship (3D QSAR) studies [Durdagi et al., J. Med. Chem.2007, 50, 2875]. The reported 3D models of the CB1 receptor allowed us to construct a new 3D QSAR model based on theoretical calculations and molecular docking studies. Statistical comparison of the constructed two 3D QSAR studies showed the improvement of the new model. In addition, the new model can explain more effectively the experimental data and thus it can serve more efficiently in the rational drug design of pharmacologically optimized CB analogues.
Durdagi
Serdar
S
Institute of Organic and Pharmaceutical Chemistry, The National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, 11635 Athens, Greece.
Papadopoulos
Manthos G
MG
Papahatjis
Demetris P
DP
Mavromoustakos
Thomas
T
D001665:Binding Sites; D002186:Cannabinoids / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism; D012984:Software
D002186:Cannabinoids; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1