Honors Theses

Date of Award

2019

Document Type

Undergraduate Thesis

Department

Chemistry and Biochemistry

First Advisor

Murrell Godfrey

Relational Format

Dissertation/Thesis

Abstract

Kratom, a plant commonly found in southeast Asia, has traditionally been used for medicinal treatments. Recently, however, the popularity of the drug has significantly increased due to its euphoric effects, leading to it being used as an alternative to illegal opioids. Several alkaloid compounds have been isolated from the leaves of the plant. The main alkaloids seen are the following five alkaloids: mitragynine, 7-hydroxymitragynine, speciociliatine, speciogynine, and paynantheine. Two alkaloids, mitragynine and 7-hydroxymitragynine, have exhibited high potencies and are potentially even more potent than morphine. Previous studies have indicated that the main mediator of the psychoactive effects is the opioid receptor system, specifically the μ-, κ-, and δ- opioid receptors. The highest binding affinities occur at the μ -opioid receptor and lesser affinities at the κ- and δ- opioid receptors. In this study, the μ -opioid receptor model was used to establish the ligand-receptor interactions between the receptors and the constituents of specific kratom alkaloids. This was accomplished using Schrodinger’s Maestro molecular modeling software. The major natural alkaloids of the plant were selected for his study because of their high abundances within the kratom plant as well as their binding affinities. Docking of the ligands to the receptor took place after both the alkaloid ligands and the opioid receptor model were prepped for docking and a grid of the active sites were generated. Data generated from each docking yielded information on the best poses/positions of the alkaloids for binding to the receptor, interactions between the ligands and receptors, and the estimated binding affinities. The study aimed to find patterns within the alkaloid structural group that would lead to the identification of key structural components and/or protein residues that are essential to binding with the μ-opioid receptor. The results of this study will lead to a new understanding of the effects kratom and its alkaloids have within the human body and help determine its potential for abuse. In addition to the results found in this study, future studies will help create a database of these alkaloids and their structures to facilitate the process of identifying them and perceiving their interactions with the μ-opioid receptor.

Available for download on Wednesday, September 02, 2020

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