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Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates
Thesis (PhD (Biochemistry))--University of Pretoria, 2023.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2024
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| _version_ | 1867613531874000896 |
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| access_status_str | Open Access |
| author2 | Birkholtz, Lyn-Marie |
| author_browse | Birkholtz, Lyn-Marie |
| author_facet | Birkholtz, Lyn-Marie |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD (Biochemistry))--University of Pretoria, 2023. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/94677 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:38.105Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/94677 Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates Birkholtz, Lyn-Marie mariskanaude@gmail.com Naude, Mariska UCTD Gametocyte Antimalarial compound Cheminformatics Transport Plasmodium Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Natural and agricultural sciences theses SDG-03 SDG-09: Industry, innovation and infrastructure Natural and agricultural sciences theses SDG-09 Thesis (PhD (Biochemistry))--University of Pretoria, 2023. Malaria drug discovery initiatives are driven by concerns regarding the emergence of parasite resistance to current antimalarials and require novel compounds with the ability to target both the pathogenic and transmissible stages of the human malaria parasite, Plasmodium falciparum. These individual stages respond differently to compounds with majority affecting asexual blood stage (ABS) parasites and a loss in activity observed against gametocytes. This study investigated the compounding factors associated with stage-specific vs. multistage activity of antiplasmodial compounds. Here, it was observed that there is a threshold for loss of activity from ABS parasites to gametocytes to effectively kill gametocytes populations with dosing based on in vitro ABS activity. Moreover, compounds with immature gametocyte activity are of utmost importance to ensure complete clearance of gametocytes and therefore block transmission. To improve the development of compounds with gametocyte activity, the mechanistic causes of these differential activities were investigated. We showed for the first time that gametocytocidal activity is driven by their distinct physicochemical properties that allow for effective uptake into gametocytes. Therefore, this study provides a comprehensive analysis as to the required profiles of potential multistage active antimalarial agents and facilitate the development of effective transmission-blocking compounds. DAAD-NRF JOINT IN-COUNTRY SCHOLARSHIP PROGRAMME (UID: 117805) Medicines for Malaria Venture (LMB: RD-19-001) South African Medical Research Council and the Department of Science and Innovation South African Research Chairs Initiative Grants managed by the National Research Foundation (LMB UID: 84627) The University of Pretoria Institute for Sustainable Malaria Control acknowledges the South African Medical Research Council as Collaborating Centre for Malaria Research Biochemistry PhD (Biochemistry) Unrestricted Faculty of Natural and Agricultural Sciences 2024-02-16T07:45:28Z 2024-02-16T07:45:28Z 2024-04 2023-12-11 Thesis * A2024 http://hdl.handle.net/2263/94677 10.25403/UPresearchdata.25226171 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Gametocyte Antimalarial compound Cheminformatics Transport Plasmodium Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Natural and agricultural sciences theses SDG-03 SDG-09: Industry, innovation and infrastructure Natural and agricultural sciences theses SDG-09 Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| title | Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| title_full | Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| title_fullStr | Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| title_full_unstemmed | Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| title_short | Systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| title_sort | systematic biochemical and cheminformatic evaluation of the gametocytocidal activity of antimalarial lead candidates |
| topic | UCTD Gametocyte Antimalarial compound Cheminformatics Transport Plasmodium Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Natural and agricultural sciences theses SDG-03 SDG-09: Industry, innovation and infrastructure Natural and agricultural sciences theses SDG-09 |
| url | http://hdl.handle.net/2263/94677 |