In silico Toxicity and Pharmaceutical Properties to Get Candidates for Antitumor Drug

Background: Drug metabolism is a crucial aspect of medical practice and pharmacology, involving the transformation of drugs by various bodily systems to create compounds that are more easily eliminated from the body. Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, poor pharmacokinetic properties such as limited water solubility, rapid elimination and metabolism lead to low bioavailability, restricting its further clinical application. Rosmarinic acid, soluble in ethanol and found in Rosemary leaves, has demonstrated therapeutic benefits in conditions such as cancer, diabetes, inflammatory disorders, neurodegenerative disorders, and liver disease.
Method: In silico is a term for experiments or tests carried out using computer simulation methods. In silico testing has emerged as a valuable approach for initiating the exploration of novel drug compounds or enhancing the efficacy of existing ones. This method involves predicting, generating hypotheses, and uncovering potential breakthroughs in medicine and therapy through virtual simulations.
Results: Caco2 value of Sorafenib ligand as a comparison, namely 0.762. The highest Caco2 value is owned by Betulinic Acid and the value The lowest Caco2 is owned by Rosmarinic Acid. The highest sample HIA value was owned by Ursolic Acid and the lowest was owned by Rosmarinic Acid. Meanwhile, Sorafenib's HIA value is 85,494. ligands such as Carnosol and rosmanol have a high distribution volume, while the Sama carnosic league, ursolic acid and betulinic acid have a low distribution volume. The Rosmarinic acid ligand has a good distribution volume of 0.393, while the distribution volume value of Sorafenib is -0.009. The highest BBB sample value was owned by Carnosol and the lowest was owned by Rosmarinic acid. Meanwhile, the comparison ligand has a value of -1.473 and is considered less distributed in the brain. all ligands such as Carnosic Acid, Carnosol, Rosmanol, Ursolic Acid, Betulinic Acid, Rosmarinic acid do not have mutagenicity and Cytotoxic effects, but have an effect on immunity. The comparison ligand Sorafenib turned out to have effects on hepatotoxicity, immunity and cytotoxicity.
Conclusion: In pharmacokinetic research, the six phenolic acid compounds in Rosemary exhibited superior properties compared to the reference ligand Sorafenib.

背景：药物代谢是医学实践和药理学中的一个关键方面，涉及通过各种身体系统对药物进行转化，以生成更易于从体内排除的化合物。索拉非尼被报道为一种有用的辅助治疗药物，适用于接受手术切除的肝细胞癌患者。然而，其药代动力学特性不佳，如有限的水溶性、快速消除和代谢，导致生物利用度低，限制了其在临床应用中的进一步推广。迷迭香酸，一种可溶于乙醇并存在于迷迭香叶片中的化合物，已在癌症、糖尿病、炎症性疾病、神经退行性疾病和肝病等疾病中显示出治疗益处。
方法：计算机模拟实验或测试被称为‘在硅上’（In silico）。‘在硅上’测试已成为探索新型药物化合物或提高现有药物疗效的有价值方法。此方法涉及通过虚拟模拟预测、生成假设并揭示医学和疗法中的潜在突破。
结果：以索拉非尼配体的Caco2值为比较，即0.762。贝塔酸（Betulinic Acid）具有最高的Caco2值，而迷迭香酸（Rosmarinic Acid）具有最低的Caco2值。具有最高样本HIA值的是熊果酸（Ursolic Acid），最低的是迷迭香酸。同时，索拉非尼的HIA值为85,494。如卡诺索尔（Carnosol）和罗索曼醇（rosmanol）等配体具有高分布体积，而萨马卡诺酸（Sama carnosic league）、熊果酸和贝塔酸具有低分布体积。迷迭香酸配体具有良好的分布体积0.393，而索拉非尼的分布体积值为-0.009。具有最高BBB样本值的是卡诺索尔，最低的是迷迭香酸。同时，比较配体的值为-1.473，被认为在脑部分布较少。所有配体，如迷迭香酸、卡诺索尔、罗索曼醇、熊果酸、贝塔酸和迷迭香酸，均不具有致突变性和细胞毒性，但对免疫系统有影响。比较配体索拉非尼最终显示出对肝毒性、免疫和细胞毒性的影响。
结论：在药代动力学研究中，迷迭香中的六种酚酸化合物相对于参考配体索拉非尼表现出卓越的特性。