A Comprehensive Modeling of Bioenhancers Docked to Transport Proteins to Enhance Bioavailability
DOI:
https://doi.org/10.47611/jsrhs.v11i4.3727Keywords:
Docking, ABC transport proteins, P-Glycoprotien, Bioenhancers, FlavonoidsAbstract
With pharmaceutical availability being a pertinent issue in modern medicine, the ability of bioenhancers to increase the bioavailability of a drug, thereby reducing the required dosage, can be critical for reducing treatment costs. Flavonoids, one form of bioenhancers, are metabolites that increase the availability through inhibition of key proteins in gut epithelial cells and transport proteins. Bioenhancers have the potential to inhibit proteins that limit absorption, thus increasing the amount of a target drug that can enter systemic circulation, increasing bioavailability. P-glycoprotein (P-gp) is one of the membrane transport proteins whose function is to transport drugs in and out of the cell. Human serum albumin (HSA), the most abundant protein in the human plasma, is a protein that serves to transport several signals and other compounds throughout the circulatory system. This study assessed the binding of various bioenhancers (piperine, quercetin, capsaicin, naringin, genistein, lysergol, sinomenine, tangeretin) to various forms of P-gp, HSA and ABC transporters to improve drug bioavailability. We hypothesized that the bioenhancers would bind to these transport proteins, thereby inhibiting them and increasing bioavailability.An examination of the geometric shape complementarity scores in PatchDock and the binding affinities (ΔG kcal/mol) from three other web servers (Webina, DockThor, CB-Dock) showed that naringin produces the most optimal binding scores overall. Given the promising optimal binding scores, the data provides critical insight into administering bioenhancers with drugs to improve bioavailability, as well as suggesting that naringin may be a valuable compound to conduct further tests in vitro and in vivo.
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