Analytical, biological and chemical investigations on selected classes of alkaloids
This PhD project focuses on the phytochemical, antiviral and analytical investigation of selected classes of alkaloids. The thesis contains two distinct parts; the first one dealing with Amaryllidaceae alkaloids and potential antiviral agents, more in particular against SARS-CoV-2; and the second one dealing with quality control of alkaloid-containing food supplements based on Maca (Lepidium meyenii). A general structure elucidation workflow was established, combining the power of computer-assisted structure elucidation (CASE) by DFT (density functional theory) calculations with various chromatographic and spectroscopic techniques. The workflow was successfully applied to determine 2D and 3D structures of all compounds in this study. In addition, the structure of a mistakenly assigned compound named “macaridine” was revised to macapyrrolin C by DFT calculation of chemical shifts. The phytochemical investigations of the four plant species (Hymenocallis littoralis, Pancratium maritimum, Scadoxus multiflorus, Lepidium meyenii) led to the discovery of nine novel alkaloids as well as extended the phytochemical profiles of the plant species. A library of Amaryllidaceae alkaloids was built and screened in vitro against the emerging SARS-CoV-2 and cytotoxicity on Vero-E6 cell line. As a result, thirteen compounds displayed moderate inhibition of SARS-CoV-2 replication (EC50 = 39 – 100 µM); ten compounds were devoid of activity and cytotoxicity, and twelve compounds lacked selective activity, since they were cytotoxic. Preliminary evaluation of structure-activity relationships revealed four skeleton-types (lycorine, homolycorine, crinine, and galanthamine) as promising scaffolds for further research. A new UPLC-TQD-MS/MS method was developed and validated for quality control of alkaloids in Maca-containing food supplements, because of their suspected toxicity. This represents the first analytical method for this purpose. Results obtained from analyses of commercial products indicate the alkaloid content of 500 – 600 ppm in pure Maca powder. From a regulatory point of view, and based on safety concerns about the alkaloidal constituents of L. meyenii, it may be advisable to establish a maximum level of particular alkaloids or alkaloid classes in food supplements containing Maca, rather than to request their total absence. Also, we recommend the use of lepidilines as chemical markers for characterization of Maca in all types of commercial preparation due to their high content, exclusive existence in Maca and ultra-sensitivity to MS detection.
Antwerp : University of Antwerp, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Department of Pharmaceutical Sciences , 2023
217 p.
Supervisor: Pieters, L. [Supervisor]
Supervisor: Tuenter, E. [Supervisor]
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Creation 26.10.2023
Last edited 10.11.2023
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