Investigation of binding interaction behavior between antiemetic drugs and Trypsin by spectroscopy and molecular docking

Antiemetic drugs are used to control excessive vomiting and nausea and generally absorbed through gastrointestinal tract. In present study, the in-vitro binding interactions two of the antiemetic drugs (dimen-hydrinate and ondansetron) between Trypsin (Tsn) secreted from pancreas to small intestine for protein digestion were investigated by fluorescence emission spectroscopy (FES), UV-VIS spectroscopy, synchronous fluorescence spectroscopy (SFS), FT-IR spectroscopy and molecular modeling methods. Also, the effect of these drugs on the catalytic activity of Tsn was determined. The fluorescence quenching experiments indicated that each drugs quenched the intrinsic fluorescence of Tsn with their increased concentrations. The results of SFS and UV-VIS spectra proved the interaction of dimenhydrinate and ondansetron with Tsn. FT-IR spectra showed that the secondary structure of enzyme was altered in the presence of the drugs. All these spectroscopy results were validated and explained by molecular docking studies. Both drugs have inhibition effect on the catalytic activity of Tsn and the IC50 values were determined as 2.6 x 10(-4) M and 6.4 x 10(-4) M for dimenhydrinate and ondansetron, respectively. Docking results revealed that the hydrogen bond interaction of dimenhydrinate with active-site residue Ser195 and ondansetron with active-site residues His57 and Ser195 hydrogen bonds might be cause the inhibition of enzyme activity. The results of this study can provide valuable information in the field of pharmacokinetics and pharmacodynamics. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the binding interactions between two antiemetic drugs and Trypsin using various spectroscopy techniques and molecular modeling methods. The results showed that both drugs quenched the intrinsic fluorescence of Tsn and affected the enzyme's structure and catalytic activity. The findings provide valuable information for pharmacokinetics and pharmacodynamics research.