Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines.
Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines.
Asian Pac J Cancer Prev. 2024 Mar 1;25(3):839-856. doi: 10.31557/APJCP.2024.25.3.839.
The purpose of this study is to comparatively analyze the anticancer properties of Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabivarin (THCV) using In silico tools.
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.
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.
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.
本研究旨在通过计算工具比较分析四氢大麻酚（THC）、大麻二酚（CBD）和四氢大麻素（THCV）的抗癌特性。
使用 SwissADME 和 pkCSM 评估大麻素的物理化学和药代动力学特性。利用 Protox-II 评估它们的细胞毒性。还使用 Way2Drug Predictive Server 预测大麻素的化学 - 生物相互作用，该服务器包括急性大鼠毒性、Adver-Pred、CLC-Pred 和 Pass Target Prediction。
使用 SwissADME 进行的物理化学和药物相似性分析都有利于 THCV，因为它具有高水溶性和较低的 MLOGP 值。另一方面，ADMET 评估表明 THC 和 CBD 具有良好的皮肤渗透性，而 THC 和 THCV 均表现出更好的 BBB 渗透性和对 CYP1A2 酶的低抑制活性。此外，Protox-II 的毒性预测表明 CBD 发生肝毒性、致癌性和免疫毒性的可能性最低。相反，它发生致突变性和细胞毒性的可能性最高。此外，CLC 结果表明 CBD 对肺癌的可能性最高。大鼠毒性预测表明，在三种大麻素中，THCV 在大鼠口服和 IV 中的 LD50 浓度最低。
总体而言，三种大麻素化合物的计算机预测表明它们是口服药物制剂的良好候选物。在这三种大麻素中，THCV 在药物相似性和 ADMET 分析、药理学特性评估和细胞毒性评估结果方面具有最有利的结果，是未来化疗的优秀抗癌候选物。需要进一步研究化合物的生物评价，以阐明它们的潜在药理活性。
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