In Silico Assessment of Drug-Like Properties of Phytocannabinoids in Cannabis Sativa

Abstract

This study investigated drug-like properties of phytocannabinoids in Cannabis sativa using an in silico study. We report sixteen phytocannabinoids: cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabinodiol (CBDL), cannabielsoin (CBE), cannabitriol (CBT), Δ9-tetrahydrocannabinol (Δ9-THC), Δ9-tetrahydrocannabivarin (Δ9-THCV), and Δ8-tetrahydrocannabinol (Δ8-THC). All chemical structures and properties were obtained from PubChem Compound, National Center for Biotechnology Information, U.S. National Library of Medicine. Molinspiration was used for the calculation of molecular properties and bioactivity score. The parameters were molecular weight (MW), number of hydrogen acceptor (HBA), number of hydrogen donor (HBD), partition coefficient (cLogP), polar surface area (PSA) and number of rotatable bonds (NROTB). We predicted bioactivity scores for G Protein-Coupled Receptors (GPCR) ligand, ion channel modulator, kinase inhibitor, nuclear receptor ligand, protease inhibitor and enzyme inhibitor. Lipinski's rule was used as reference to determine the drug-like properties of the phytocannabinoids. All compounds have MW<500, HBA<10, HBD<5, TPSA<140Å 2 and NRTOB<10. Bioactivity score showed an active or moderately active in all compounds. Fifteen compounds were detected to have one violation. CBT did not violate any of the Lipinski's Ro5 and demonstrated as a good drug-like property and for oral absorption. This suggests that CBT can be further tested for potential orally active drugs.

Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review

“…In the investigation of drug-like properties of phytocannabinoids by an in silico study [ 272 ], compounds including CBD, CBDA, CBC, CBG, CBN, THC, and many others, were found to have molecular weights of <500, a number of hydrogen acceptors (HBA) <10, a number of hydrogen donors (HBD) <5, a topological polar surface area (TPSA) <140 Å 2 and a number of rotatable bonds (NRTOB) <10. They were found to have moderate to active bioactivity scores, except for CBDA and CBT, and all showed good oral absorption with a 100% absorptivity.…”

(‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research

“…Recent in silico study was carried out to investigate drug-like properties of CBDA and other phytocannabinoids [50]. Molecular properties, such as number of hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD), partition coefficient (cLogP), polar surface area (PSA), and the number of rotatable bonds (NROTB), were calculated using Molinspiration Cheminformatics software (Table 1).…”

“…CBDA's topological PSA (TPSA) was in line with an absorptivity of more than 90%. Furthermore, when drug likeness score for G protein-coupled receptors (GPCRs) ligands, ion channel modulators, kinase inhibitors, nuclear receptor ligands, and protease inhibitors were predicted, it was observed that CBDA is moderately active in all bioactive scores [50]. Unfortunately, the more recent drug discovery approach for in silico pharmacokinetic profile did not consider CBDA among the compounds investigated to get structural insights into the selection of cannabinoid scaffolds for the development of antitumor drugs [51].…”

Exploring Cannabis sativa L for Anti-Alzheimer Potential: An extensive Computational Study including Molecular Docking, Molecular Dynamics, and ADMET Assessments

“…Many investigations have examined the potential bene ts of cannabis in addressing neurodegenerative diseases that affect cognitive abilities [20][21][22][23][24][25][26]. Additionally, the neuroprotective effect of this plant is widely studied and proven [27].…”