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. 2024 Mar 1;25(3):839-856.
doi: 10.31557/APJCP.2024.25.3.839.

A Comparative Analysis on the Potential Anticancer Properties of Tetrahydrocannabinol, Cannabidiol, and Tetrahydrocannabivarin Compounds Through In Silico Approach

Angelica A Gallardo  1 , Mikaela Rose Gutierrez  1 , Lyka Alexandrea J Gomez  1 , Patricia Arielle O Delos Reyes  1 , Sophia Allison A Dones  1 , Maria Mikaela U Dumbrique  1 , Heather Eena Lim  1 , Maria Isabel H Liquido  1 , Mary Margaret L Macawile  1 , Ella Denese Anne B Maglaqui  1 , Angelica Mae G Manalo  1 , Mark Kevin P Devanadera  1   2 , Alexis M Labrador  1
Affiliations

A Comparative Analysis on the Potential Anticancer Properties of Tetrahydrocannabinol, Cannabidiol, and Tetrahydrocannabivarin Compounds Through In Silico Approach

Angelica A Gallardo et al. Asian Pac J Cancer Prev. .

Abstract

Objective: The purpose of this study is to comparatively analyze the anticancer properties of Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabivarin (THCV) using In silico tools.

Methods: Using SwissADME and pkCSM, the physicochemical and pharmacokinetics properties of the cannabinoids were evaluated. Protox-II was utilized for the assessment of their cytotoxicity. The chemical-biological interactions of the cannabinoids were also predicted using the Way2Drug Predictive Server which comprises Acute Rat Toxicity, Adver-Pred, CLC-Pred, and Pass Target Prediction.

Results: Both physicochemical and drug-likeness analysis using SwissADME favored THCV due to high water solubility and lower MLOGP value. On the other hand, ADMET assessment demonstrated that THC and CBD have good skin permeability while both THC and THCV exhibited better BBB permeability and have low inhibitory activity on the CYP1A2 enzyme. Furthermore, toxicity predictions by Protox-II revealed that CBD has the lowest probability of hepatotoxicity, carcinogenicity, and immunotoxicity. Contrarily, it has the highest probability of being inactive in mutagenicity and cytotoxicity. Additionally, CLC results revealed that CBD has the highest probability against lung carcinoma. The rat toxicity prediction showed that among the cannabinoids, THCV had the lowest LD50 concentration in rat oral and IV.

Conclusion: Overall, in silico predictions of the three cannabinoid compounds revealed that they are good candidates for oral drug formulation. Among the three cannabinoids, THCV is an excellent anticancer aspirant for future chemotherapy with the most favorable results in drug-likeness and ADMET analysis, pharmacological properties evaluation, and cytotoxicity assessment results. Further study on bioevaluation of compounds is needed to elucidate their potential pharmacological activities.

Keywords: ADME; Anticancer drugs; Cytotoxicity; Virtual screening; cannabinoids.

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Conflict of interest statement

All authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Schematic Representation of Anticancer Properties Assessment of Phytocannabinoids (THC, CBD, & THCV) Compounds Using in silico Approach
Figure 2
Figure 2
Molecular Structures of THC, CBD, and THCV
Figure 3
Figure 3
Schematic Diagram of Bioavailability Radar for Drug likeness of THC, CBD, and THCV (lipophilicity: XLOGP3 between +5.89 and +6.97, size: MW between 286.41 and 314.46 g/mol, polarity: TPSA between 29.46 and 40.46 Å2, solubility: log S not higher than 6, saturation: fraction of carbons in the sp3 hybridization not less than 0.25, and flexibility: no more than 9 rotatable bonds)
Figure 4
Figure 4
Schematic Representation of Perceptive Evaluation of Passive Gastrointestinal Absorption (HIA) and Blood-Brain Barrier (BBB) Penetration of THC, CBD, and THCV in the WLOGP-versus-TPSA using BOILED-Egg. High probability of GIT passive absorption is represented by the white region, whereas the yellow region (yolk) represents the high probability of BBB penetration. In addition, the blue dot indicator of the molecule shows that the molecule is actively effluxed by P-glycoprotein, represented as (PGP+), whereas the red color indicator shows the non-substrate of P-gp, represented as (PGP−)
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