Computational Prediction Of The Pharmacokinetics, Bioactivity And Toxicity Parameters Of The Local Anesthetic Ambucaine

Abstract

Computer aided drug design plays an important role in drug discovery and development and has become an essential tool in the pharmaceutical industry. In the present research study, the free online computational program Molinspiration Cheminformatics Toolkit (http://www.molinspiration.com) was used to evaluate the pharmacokinetic properties of ambucaine based on Lipinski's rule of five. Miscreen (http://www.molinspiration.com), a molinspiration virtual screening engine, was used to calculate bioactivity scores for ambucine. This computational tool is used to find ligands that modulate GPCRs, ion channels, nuclear receptors, and to identify kinase inhibitors, protease inhibitors, and enzyme inhibitors.

The molecular properties of ambucaine were calculated using Molinspiration Cheminformatics and the data are shown in the table. Ambucaine drug similarity was evaluated by Lipinski's rule of five, which deals with four simple physicochemical parameters (log P ≤ 5, molecular weight ≤ 500, number of hydrogen bond acceptors ≤ 10, number of hydrogen bond donors ≤ 5). Log P measurements are used to understand the dissolution behavior of a substance and thus its oral absorption and bioavailability. Ambucaine has a log P value of 3.47, indicating that it is highly lipophilic or hydrophobic. Therefore, we identify a better distribution of ambucaine after absorption in the body. The molecular weight of ambucaine was 308.42, which is within the range of ≤500. Compounds with low molecular weight are easily absorbed, distributed and transported compared to compounds with high molecular weight >500. Ambucaine also has an appropriate number of hydrogen bond acceptors and hydrogen bond donors, i.e. 2 and 5, to ensure efficient interaction with the hydrogen bond groups of refractory receptors. 10 number of rotatable bond in ambucaine explains the flexibility and conformational changes of ambucaine upon binding to receptors. It is accepted that the number of rotatable bonds should be 10 or less to confer oral bioavailability. The TPSA value of 64.80 for ambucaine shows a good intestinal absorption and blood-brain barrier penetration rate. In addition, ambucaine does not violate Lipinski's parameters, making it a drug-like molecule.

The Ambucaine has exhibited calculated bioactivity score -0.01 for GPCR ligand, 0.09 for Ion channel modulator, -0.03 for Kinase inhibitor, -0.10 for nuclear receptor ligand, -0.11 for Protease inhibitor, and -0.02 for Enzyme inhibitor.