Determination of the Negative Allosteric Binding Site of Cannabidiol at the CB1 Receptor: A Combined Computational and Site-Directed Mutagenesis Study.

Cannabinoid receptor 1 (CB1R) has been extensively studied as a potential therapeutic target for various conditions, including pain management, obesity, emesis, and metabolic syndrome. Unlike orthosteric agonists such as Δ-tetrahydrocannabinol (THC), cannabidiol (CBD) has been identified as a negative allosteric modulator (NAM) of CB1R, among its other pharmacological targets. Previous computational and structural studies have proposed various binding sites for CB1R NAMs.

A Combined Approach for Rapid Dereplication of Herb-Drug Interaction Causative Agents in Botanical Extracts-A Molecular Networking Strategy To Identify Potential Pregnane X Receptor (PXR) Modulators in Yohimbe.

Despite promising preliminary biology, natural products isolation efforts may be confounded when the active compound is not isolated during bioassay-guided purification or classical pharmacognostic research investigations. A more rational isolation procedure connecting the polypharmacology of an herb to its individual constituents must be applied to better detect bioactive molecules before tedious analytical steps are considered. While (yohimbe) has been traditionally used in herbal medicine as a general tonic, an aphrodisiac, a performance enhancer, and an integral part of various dietary supplements, the hydroethanolic extract of yohimbe was identified to possess at least 3-4-fold induction of the pregnane X receptor (PXR) at 30 μg/mL, a key nuclear receptor implicated in adverse interactions, .

iso-Guttiferone J and Structure Revision of Guttiferone J from Garcinia gummi-gutta: A Combined Experimental and Integrated QM/NMR Approach.

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from , and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.

Machine learning and traditional QSAR modeling methods: a case study of known PXR activators.

Pregnane X receptor (PXR), extensively expressed in human tissues related to digestion and metabolism, is responsible for recognizing and detoxifying diverse xenobiotics encountered by humans. To comprehend the promiscuous nature of PXR and its ability to bind a variety of ligands, computational approaches, viz., quantitative structure-activity relationship (QSAR) models, aid in the rapid dereplication of potential toxicological agents and mitigate the number of animals used to establish a meaningful regulatory decision.