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

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.

Molecular Docking and in silico Pharmacological Screening of Oleosin from Cocos Nucifera Complexed with Tamoxifen in Developing Potential Breast Chemotherapeutic Leads.

OBJECTIVE: Tamoxifen is a widely used drug for breast cancer therapy; however, concerns and controversies regarding its efficiency arise as it induces various side effects, including endometrial cancer. This study aimed to assess the application of Oleosin as a potential protein carrier of Tamoxifen by evaluating the pharmacokinetic and pharmacological properties of Tamoxifen and determining its intermolecular interactions with Oleosin through in silico techniques. METHODS: The pharmacokinetic and pharmacological properties of Tamoxifen were assessed by using predictive applications such as SwissADME, PaccMann, and Way2Drug. On the other hand, Oleosin does not have a crystal structure in PDB. Thus, homology modeling was done through SWISS-MODEL to obtain a structure. The interactions between Oleosin (Accession no.: AZZ09171.1) and Tamoxifen (PubChem ID: 2733526) were studied by performing molecular docking using AutoDock4 to determine their feasibility as breast cancer drug combinations. RESULT: The chosen structure of Oleosin from the homology modeling resulted in an RMSD of 1.80Å. Tamoxifen was predicted to have the highest activity in MCF7 cell lines, direct interaction with cytochrome enzymes, mediated interaction with estrogen receptors and tyrosine-protein kinase FYN, and low toxicity hazards based on the acute rat toxicity assay. It has lowest binding affinity of -5.26 kcal/mol. The hydrophobic (Ala106, Leu77, Ile80, Val84, and Tyr81) and electrically charged (Lys107 and Asp108) amino acids were critical in binding in the Oleosin-Tamoxifen-complex. Heatmap revealed that phenyl, ether, amine, and alkenyl are the functional groups involved in the receptor-ligand interactions. CONCLUSION: The application of Oleosin as a potential drug carrier was demonstrated by assessing the intermolecular interactions between the Tamoxifen and Oleosin through molecular docking. The properties of Tamoxifen revealed that the molecular targets impact the efficiency and the mechanism of action of the drug. This can also be the basis for investigating and determining the serious adverse effects induced by the drug.