Title page for ETD etd-09202010-113318


Document Type Master's Dissertation
Author Makgatho, Ephraim Marema
URN etd-09202010-113318
Document Title Flow cytometric evaluation of riminophenazines as antimalarial agents
Degree MSc
Department Pharmacology
Supervisor
Advisor Name Title
Prof R Anderson Co-Supervisor
Prof C E Medlen Supervisor
Keywords
  • plasmodium falciparum
  • clofazimine
  • antimalarial
Date 1996-04-01
Availability unrestricted
Abstract
The in vitro antimalarial activity of clofazimine and seven of its analogues, all TMP(tetramethyl-piperidyl group)-derivatives except 8669, against the R8-1 and pfUP-1 laboratory strains of Plasmodium falciparum was investigated using a flow cytometric procedure. The flow cytometric method was compared with microscopy and radiometry for efficiency in quantitating the level of parasitemia in malaria cultures. The flow cytometric method compared well, as determined by the 81and and Altman measure of agreement, with both microscopy and radiometry and was chosen for use in this study due to its speed, precision and convenience (includes a fixing step that allows samples to be evaluated at anyone time). The riminophenazine agents were found to exhibit antimalarial action of varying degrees: B669, B4100, B4103, B4112 and B4158 showed the best activity followed by B4121 and B4169. Clofazimine did not exhibit any activity at concentrations up to 2g/ml in this system. Their effective concentrations in vitro were comparable to that of standard antimalarial agents such as chloroquine. The agents B4103 and B4112 exhibited additive antimalarial activities when combined with chloroquine. The inclusion of the TMP group and extent of halogenation of six of the riminophenazines tested indicate that it is these structural properties which are the major determinants of the antiplasmodial activity. This is the first study to establish an antiplasmodial activity of riminophenazines and further tests are necessary to establish their antiparasitic mode of action and therapeutic potential in animal models of experimental chemotherapy.

1996 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.

Please cite as follows:

Makgatho, EM 1996, Flow cytometric evaluation of riminophenazines as antimalarial agents, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-09202010-113318/ >

H1077/ag

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