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

Abstract

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.