Bioactivity of the cannabigerol cannabinoid and its analogues – the role of 3-dimensional conformation
Mohammed S. Salha, Henry Adenusi, John H. Dupuis, Enrico Bodo, Bruno Botta, Iain McKenzie, Rickey Y. Yada, David H. Farrar, Jakob Magolan, Kun Tian, Gregory A. Chass
Abstract
-substituted hydroxyl groups as well as CH⋯π interactions with the aromatic density of the ring itself, among other interactions. Although weakly polar, these interactions are structurally and dynamically influential, effectively 'stapling' the ends of the chains to the central ring structure. Molecular docking of the differing 3-D poses of CBG to cytochrome P450 3A4 resulted in lowered inhibitory action by the coiled conformers, relative to their fully-extended counterparts, helping explain the trends in the inhibition of the metabolic activity of the CYP450 3A4. The approach detailed herein represents an effective method for the characterisation of other bioactive molecules, towards improved understanding of their QSARs and in guiding the rational design and synthesis of related compounds.