<em>In silico</em> pharmacokinetic and toxicological study of Cinnamic Acid analogues

Abstract

Cinnamic acid analogs are natural phenolic compounds that have a wide range of biological and therapeutic activities. The present work aimed to predict, through in silico methodologies, the oral bioavailability and pharmacokinetic and toxicological analyzes for four cinnamic acid analogues (caffeic acid, ferulic acid, p-coumaric acid and synaptic acid). The study revealed that the analogues have good oral bioavailability, favorable pharmacokinetic and toxicological parameters. The Virtual Screening performed to predict oral bioavailability indicated that all analogues do not violate Lipinski's Rule. The in silico ADME study of pharmacokinetic parameters showed that all derivatives have high intestinal absorption, are permeable by Caco-2 cells, do not cross the blood-brain barrier, do not inhibit P-glycoprotein. There will be no inhibition of the cytochrome P450 complex isoenzymes (CYP450). The in silico Toxicological study revealed that the analogues do not have toxicity by the AMES Test, are not carcinogenic and do not present acute oral toxicity.

In silico pharmacokinetic and toxicological evaluation of Cephalonium antibiotic in human and environmental health

“…In pharmacokinetic terms, human intestinal absorption (HIA) represents the sum of the absorption rate and the absolute bioavailability of the drug that reaches the systemic circulation, since when administered orally, the concentration of the drug will always be less than 100% due to the incomplete extension in the process of absorption and elimination of the first-pass effect in the liver (hepatic biotransformation). Thus, the % HIA represents the percentage of dose of the active principle that was administered orally and that reaches the hepatic portal system (HOU, 2008), (ARAUJO et al, 2022), .…”

“…The permeability of chemical compounds through the blood-brain barrier (BBB) consists of passing through endothelial cells that have tight and compacted junctions, which considerably restricts the permeability of the compounds, ensuring that the drug candidate does not cross the BBB, otherwise, it would increase considerably the probability of having side effects (adverse effects) (THOMAS, 2003). In the capillary endothelia of cerebral vessels, the presence of P-glycoprotein is essential, as it acts as a defense mechanism capable of pumping back into the blood the xenobiotic chemical substances that could eventually cross the blood-brain barrier (ARAUJO et al, 2022), (CEZÁRIO et al, 2022), .…”

“…Hepatic metabolism is the mechanism that promotes changes in the chemical structure of the compound through biochemical reactions resulting in products called metabolites. Hepatic biotransformation, together with excretion, are pharmacokinetic components responsible for drug elimination (ARAUJO et al, 2022).…”

“…It is important to note that blood plasma, interstitial fluid, and cellular cytoplasm have high polarity. When hydrophilic drugs reach the bloodstream, they pass slowly through the hepatocyte lipid membrane in the liver without changing their chemical structure and do not have access to liver enzymes (ARAUJO et al, 2022), .…”

“…Rule takes into account the following criteria: Molecular Weight (PM), which should not exceed 500 Da (Dalton); o Log P = miLogP (logarithm of the partition coefficient), whose limit value is 5; Hydrogen Bond Donor Sites = SDLH and Hydrogen Bond Acceptor Sites = SALH, which should not exceed values 5 and 10 respectively, and the Polar Surface Topological Area (TPSA) which should be less than 140 Å 2(FARIA et al, 2023), (ARAUJO et al, 2022.…”