- Title
- Synthesis of peptidomimetic compounds as HIV-1 protease inhibitors
- Creator
- Kayembe, Jean-Pierre
- ThesisAdvisor
- Klein, Rosalyn
- ThesisAdvisor
- Kaye, Perry T
- Subject
- Protease inhibitors
- Subject
- HIV (Viruses)
- Subject
- HIV infections Treatment
- Subject
- Peptidomimetics
- Date
- 2020
- Type
- Doctoral theses
- Type
- text
- Identifier
- http://hdl.handle.net/10962/124397
- Identifier
- vital:35604
- Identifier
- DOI https://dx.doi.org/10.21504/10962/124397
- Description
- This research project has involved the design, synthesis and evaluation of novel peptidomimetics compounds as HIV-1 protease inhibitors. Here is presented one-step, two-step and three-step syntheses and the in vitro bio-assay studies of a series of fully characterized peptidomimetics as HIV-1 protease inhibitors candidate using the shortest and most cost effective synthetic routes. The first series of compounds were accessed via a synthetic elaboration of Morita-Baylis-Hillman adducts by a Michael addition with benzylamine, proline or glycine esters to afford a series of β-amino-β’-hydroxycarboxylate esters in moderate to good yields. Base-catalyzed cyclization of non-benzylated aza-Michael adducts afforded a series of coumarin-3-hydroxy-2-methylenepropanoate esters in moderate yields. The uncatalyzed direct amidation of diethyl tartrate/tartaric acid and tartaric acid osazone with selected amines/amino acids afforded a series of C2-symmetrical and unsymmetrical 1,2-dihydroxycarboxylates in moderate to very high yields. All the synthesized compounds were fully characterized using spectroscopic techniques. These conjugates, designed as potential HIV-1 inhibitors, were tested against the HIV-1 protease enzyme. A number of these ligands have exhibited inhibition levels and IC50 values comparable to ritonavir, permitting, therefore, their identification as lead compounds for the development of novel inhibitors.
- Description
- Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Format
- computer, online resource, application/pdf, 1 online resource (255 pages), pdf
- Publisher
- Rhodes University, Faculty of Science, Chemistry
- Language
- English
- Rights
- Kayembe, Jean-Pierre
- Rights
- Attribution 4.0 International (CC BY 4.0)
- Rights
- Open Access
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RU Department of Chemistry
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Pages from KAYEMBE-PhD-TR20-77_embargo 2 years.jpg | 8 MB | Adobe Acrobat PDF | View Details Download |