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Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids

Dissertation (MSc(Biochemistry))--University of Pretoria, 2006.

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Other Authors: Verschoor, Jan Adrianus
Format: Thesis
Published: University of Pretoria 2013
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access_status_str Open Access
author2 Verschoor, Jan Adrianus
author_browse Verschoor, Jan Adrianus
author_facet Verschoor, Jan Adrianus
collection Thesis
dc_rights_str_mv © 2003, 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 Dissertation (MSc(Biochemistry))--University of Pretoria, 2006.
format Thesis
id oai:repository.up.ac.za:2263/24334
institution University of Pretoria (South Africa)
last_indexed 2026-06-10T12:37:05.077Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository
publishDate 2013
publishDateRange 2013
publishDateSort 2013
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:2263/24334 Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids Verschoor, Jan Adrianus upetd@up.ac.za Sebatjane, Selaelo Ivy Drugs design Tuberculosis chemotherapy Host-parasite relationships Tuberculosis research UCTD Dissertation (MSc(Biochemistry))--University of Pretoria, 2006. The need for new anti- TB drugs is increasingly rising because of the resistance of M. tuberculosis to existing drugs. The mycobacterial cell wall serves as an impermeable protective barrier for the bacilli from toxins and chemotherapeutic agents, mainly due to the mycolic acids waxy outer layer. The mycolic acids play an important role in the architecture and physical properties of the mycobacterial cell wall. This study was based on the observed mimicry and association between the host cholesterol and the mycolic acids. This may present yet another way in which the TB bacilli survives by manipulating its host and using some of its components for its survival. The research focused on whether the cholesterol-like molecules on the mycobacterial cell surface can be targeted for effective delivery of anti-mycobacterial agents. In order to exploit the ability of M tuberculosis to accumulate cholesterol or interact with it, a cholesterol¬binding molecule was used for targeting an anti- TB drug to the mycobacterial cell wall or to the cell membrane of infected macrophages. It was observed that the drug does possess anti-mycobacterial activities even though higher concentrations of the compound were required. This supports the idea that the ability of cholesterol to interact with the mycobacterial mycolic acids can be exploited for designing of anti- TB agents. It was also demonstrated in this study that cholesterol has a negative effect on the activity of INH. Thus cholesterol, which is required for entry and survival of M tuberculosis in the host cells, has yet another protective effect on this pathogen. The possible ability of cholesterol to target the same enzyme(s) as INH is another small piece of knowledge to complete the puzzle to understanding the mode of virulence and pathogenesis of this pathogen and develop of new ways to fight the old enemy. Biochemistry unrestricted 2013-09-06T17:15:53Z 2005-05-19 2013-09-06T17:15:53Z 2004-04-24 2006-05-19 2005-05-05 Dissertation Sebatjane, SI 2003, Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://hdl.handle.net/2263/24334 > H697/ag http://hdl.handle.net/2263/24334 http://upetd.up.ac.za/thesis/available/etd-05052005-132142/ © 2003, 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 Drugs design
Tuberculosis chemotherapy
Host-parasite relationships
Tuberculosis research
UCTD
Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids
title Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids
title_full Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids
title_fullStr Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids
title_full_unstemmed Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids
title_short Anti-tuberculosis drug design based on a possible mimicry between host and pathogen lipids
title_sort anti tuberculosis drug design based on a possible mimicry between host and pathogen lipids
topic Drugs design
Tuberculosis chemotherapy
Host-parasite relationships
Tuberculosis research
UCTD
url http://hdl.handle.net/2263/24334
http://upetd.up.ac.za/thesis/available/etd-05052005-132142/