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The application of 3D-QSAR studies for novel cannabinoid ligands substituted at the C1' position of the alkyl side chain on the structural requirements for binding to cannabinoid receptors CB1 and CB2.
J Med Chem. 2007 Jun 14; 50(12):2875-85.JM

Abstract

A set of 30 novel Delta8-tetrahydrocannabinol and cannabidiol analogues were subjected to three-dimensional quantitative structure-activity relationship studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. Using a combination of molecular modeling techniques and NMR spectroscopy, the putative bioactive conformation of the most potent cannabinoid (CB) ligand in the training set was determined. This conformer was used as the template and CB1 and CB2 pharmacophore models were developed. These models were fitted with experimental binding data and gave high correlation coefficients. Contour maps of the CB1 and CB2 models of CoMFA and CoMSIA approaches show that steric effects dominantly determine the binding affinities. The CoMFA and CoMSIA analyses based on the binding affinity data of CB ligands at the CB1 and CB2 receptors allowed us to deduce the possible optimal binding positions. This information can be used for the design of new CB analogues with enhanced activity and other tailored properties.

Authors+Show Affiliations

Institute of Organic and Pharmaceutical Chemistry, The National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, 11635 Athens, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17521177

Citation

Durdagi, Serdar, et al. "The Application of 3D-QSAR Studies for Novel Cannabinoid Ligands Substituted at the C1' Position of the Alkyl Side Chain On the Structural Requirements for Binding to Cannabinoid Receptors CB1 and CB2." Journal of Medicinal Chemistry, vol. 50, no. 12, 2007, pp. 2875-85.
Durdagi S, Kapou A, Kourouli T, et al. The application of 3D-QSAR studies for novel cannabinoid ligands substituted at the C1' position of the alkyl side chain on the structural requirements for binding to cannabinoid receptors CB1 and CB2. J Med Chem. 2007;50(12):2875-85.
Durdagi, S., Kapou, A., Kourouli, T., Andreou, T., Nikas, S. P., Nahmias, V. R., Papahatjis, D. P., Papadopoulos, M. G., & Mavromoustakos, T. (2007). The application of 3D-QSAR studies for novel cannabinoid ligands substituted at the C1' position of the alkyl side chain on the structural requirements for binding to cannabinoid receptors CB1 and CB2. Journal of Medicinal Chemistry, 50(12), 2875-85.
Durdagi S, et al. The Application of 3D-QSAR Studies for Novel Cannabinoid Ligands Substituted at the C1' Position of the Alkyl Side Chain On the Structural Requirements for Binding to Cannabinoid Receptors CB1 and CB2. J Med Chem. 2007 Jun 14;50(12):2875-85. PubMed PMID: 17521177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The application of 3D-QSAR studies for novel cannabinoid ligands substituted at the C1' position of the alkyl side chain on the structural requirements for binding to cannabinoid receptors CB1 and CB2. AU - Durdagi,Serdar, AU - Kapou,Agnes, AU - Kourouli,Therapia, AU - Andreou,Thanos, AU - Nikas,Spyros P, AU - Nahmias,Victoria R, AU - Papahatjis,Demetris P, AU - Papadopoulos,Manthos G, AU - Mavromoustakos,Thomas, Y1 - 2007/05/24/ PY - 2007/5/25/pubmed PY - 2007/8/19/medline PY - 2007/5/25/entrez SP - 2875 EP - 85 JF - Journal of medicinal chemistry JO - J Med Chem VL - 50 IS - 12 N2 - A set of 30 novel Delta8-tetrahydrocannabinol and cannabidiol analogues were subjected to three-dimensional quantitative structure-activity relationship studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. Using a combination of molecular modeling techniques and NMR spectroscopy, the putative bioactive conformation of the most potent cannabinoid (CB) ligand in the training set was determined. This conformer was used as the template and CB1 and CB2 pharmacophore models were developed. These models were fitted with experimental binding data and gave high correlation coefficients. Contour maps of the CB1 and CB2 models of CoMFA and CoMSIA approaches show that steric effects dominantly determine the binding affinities. The CoMFA and CoMSIA analyses based on the binding affinity data of CB ligands at the CB1 and CB2 receptors allowed us to deduce the possible optimal binding positions. This information can be used for the design of new CB analogues with enhanced activity and other tailored properties. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/17521177/The_application_of_3D_QSAR_studies_for_novel_cannabinoid_ligands_substituted_at_the_C1'_position_of_the_alkyl_side_chain_on_the_structural_requirements_for_binding_to_cannabinoid_receptors_CB1_and_CB2_ L2 - https://doi.org/10.1021/jm0610705 DB - PRIME DP - Unbound Medicine ER -