Faculty of Arts and Sciences, Department of Chemistry, Suleyman Demirel University, Cunur, Isparta 32260, Turkey.
Faculty of Arts and Sciences, Department of Chemistry, Suleyman Demirel University, Cunur, Isparta 32260, Turkey.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Sep 5;258:119817. doi: 10.1016/j.saa.2021.119817. Epub 2021 Apr 20.
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 (dimenhydrinate 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 IC values were determined as 2.6 × 10 M and 6.4 × 10 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.
止吐药用于控制过度呕吐和恶心，通常通过胃肠道吸收。在本研究中，通过荧光发射光谱（FES）、紫外-可见光谱、同步荧光光谱（SFS）、傅里叶变换红外光谱（FT-IR）和分子建模方法研究了两种止吐药（茶苯海明和昂丹司琼）与胰腺分泌到小肠用于蛋白质消化的胰蛋白酶（Tsn）之间的体外结合相互作用。此外，还测定了这些药物对 Tsn 催化活性的影响。荧光猝灭实验表明，随着药物浓度的增加，每种药物都会猝灭 Tsn 的内源荧光。SFS 和紫外-可见光谱的结果证明了茶苯海明和昂丹司琼与 Tsn 的相互作用。FT-IR 光谱表明，在药物存在下，酶的二级结构发生了变化。所有这些光谱结果都通过分子对接研究得到了验证和解释。两种药物均对 Tsn 的催化活性具有抑制作用，茶苯海明和昂丹司琼的 IC 值分别为 2.6×10^-5 M 和 6.4×10^-5 M。对接结果表明，茶苯海明与活性部位残基 Ser195 之间的氢键相互作用以及昂丹司琼与活性部位残基 His57 和 Ser195 之间的氢键相互作用可能是导致酶活性抑制的原因。本研究结果可为药代动力学和药效学领域提供有价值的信息。
