Electronic Theses and Dissertations

Date of Award

1-1-2020

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Ikhlas A Khan

Second Advisor

David C Stevens

Third Advisor

Samir A Ross

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Studies have shown the potential risks of neurodegeneration associated with chronic consumption of plants of the Annonaceae family, which emphasize the need for further studies to identify the neurotoxic compounds in the edible annonaceous plants and compare their risk to their benefits in defeating cancer. Our study is focused on the alkaloidal constituents of two plants from the Annonaceae family, Asimina triloba and Rollinia mocusa. This study was carried out to explore the anticancer and neurotoxic constituents of the plants with the intention that separating neurotoxic constituents would help in reducing the undesirable effects of the plants if it is used as an alternative therapy. Chapter II describes the phytochemical investigation of the alkaloids from Asimina triloba twigs that yielded one new aporphine glycoside, (-)-anolobine-9-O-β-D-glucopyranoside 1, along with seven known isoquinoline alkaloids, anolobine 2, nornuciferine 3, norushinsunine 4, liriodenine 5, lysicamine 6, stepharine 7, and coclaurine 8. Alkaloids 3 and 6-8 are reported for the first time from this plant. In chapter III, the structural characteristics of eight alkaloids from methanolic extracts of dried twigs of Asimina triloba have been studied using UHPLC-QToF-MS in positive ion mode. This study described an investigation of the fragmentation pathways leading to the identification of key diagnostic fragment ions for the annonaceous alkaloids. Chapter IV demonstrates the anticancer potential and the neurotoxicity of the isolated alkaloids from Asimina triloba twigs. Six alkaloids (anolobine-9-O-β-D-glucopyranoside, anolobine, norushinsunine, liriodenine, squamolone and coclaurine) were evaluated for their anticancer potential in four human solid tumor cell lines (SK-MEL, KB, BT-549, and SK-OV-3). The potential for neurotoxicity was determined using rat cortical neurons. Three extracts, namely crude methanolic extract, alkaloids rich extract, and acetogenins rich extract, were also included in the study to explore how the presence and the absence of the alkaloids or acetogenins will affect the anticancer activity and neurotoxicity of this plant. This is the first report of anticancer activity and the neurotoxic effect of the alkaloidal constituents of Asimina triloba. Finally, chapter V describes the total synthesis of (±) anonaine, 3,4-methylenedioxy-1-phenanthreneethylamine, (±) romucosine, and [2-(3,4-methylenedioxy-1-phenanthrenyl)ethyl]-methylcarbamate by using direct arylation reactions with 3,4-methylenedioxyphenethylamine 1 and 2-bromophenylacetic acid 2 in the preparation of aporphine analogues. The presence of the synthesized compounds in Rollinia mucosa seeds and fruits was verified through the analytical technique using UHPLC-QToF-MS. All synthesized compounds were subjected to the biological evaluation to understand how they induce or reduce the cytotoxicity as well as neurotoxicity. Improved accuracy and precision of the bioactive marker compounds and natural toxins in the edible plants, dietary supplement, and natural health products will be helpful to the regulatory agencies.

Available for download on Tuesday, August 31, 2021

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