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Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues
Includes bibliographical references.
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| Main Author: | |
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Chemistry
2014
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| _version_ | 1867613217898889216 |
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| access_status_str | Open Access |
| author | Ongarora, Dennis Sure Bagwasi |
| author2 | Chibale, Kelly |
| author_browse | Chibale, Kelly Ongarora, Dennis Sure Bagwasi |
| author_facet | Chibale, Kelly Ongarora, Dennis Sure Bagwasi |
| author_sort | Ongarora, Dennis Sure Bagwasi |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/9309 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:38.580Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Department of Chemistry |
| publisherStr | Department of Chemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/9309 Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues Ongarora, Dennis Sure Bagwasi Chibale, Kelly Masimirembwa, Collen Includes bibliographical references. Malaria is a major cause of morbidity and mortality globally, resulting in over 200 million cases and 650, 000 deaths in 2010 according to the 2012 WHO Malaria Report. Furthermore, malaria endemicity is associated with poor economic growth. One of the greatest challenges facing malaria chemotherapy is the emergence of Plasmodium strains resistant to all known clinically used antimalarials. This underscores the need for the development of new drugs that retain efficacy against the resistant parasites. In this study, analogue-based drug design was employed as a form of drug ‘rescue’ in the development of novel potential antimalarials. The main aim was to design and synthesize analogues of the 4-aminoquinoline drug amodiaquine with potentially improved safety and efficacy profiles using prior knowledge of the drug metabolism and pharmacokinetics (DMPK), toxicity and efficacy profile of the drug. A representative set of compounds in four different series was synthesized in which the 4-aminoquinoline ring was coupled with benzothiazole, benzimidazole, benzoxazole and pyridyl rings bearing different aliphatic amines and diamines. The chemistry involved aromatic nucleophilic substitution reactions and hydrogenation of nitro aromatic compounds. Benzothiazole and benzoxazole analogues with a tertiary protonatable nitrogen were found to possess potent antiplasmodial activity against the drug resistant W2 and K1 Plasmodium falciparum strains. 2014-11-07T09:20:31Z 2014-11-07T09:20:31Z 2014 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/9309 eng application/pdf Department of Chemistry Faculty of Science University of Cape Town |
| spellingShingle | Ongarora, Dennis Sure Bagwasi Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues |
| thesis_degree_str | Doctoral |
| title | Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues |
| title_full | Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues |
| title_fullStr | Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues |
| title_full_unstemmed | Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues |
| title_short | Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues |
| title_sort | antimalarial drug rescue through safety improvement design synthesis and evaluation of amaodiaquine analogues |
| url | http://hdl.handle.net/11427/9309 |
| work_keys_str_mv | AT ongaroradennissurebagwasi antimalarialdrugrescuethroughsafetyimprovementdesignsynthesisandevaluationofamaodiaquineanalogues |