Document Type Master's Dissertation Author De Bruin, Jurgens Jacobus URN etd-08112009-141406 Document Title Discovery and characterization of polyamine analogues as inhibitors of the Plasmodium falciparum polyamine pathway using cheminformatics Degree Msc Department Biochemistry Supervisor
Advisor Name Title Prof F Joubert Supervisor Keywords
- chemical data
- drug molecules
Date 2009-04-15 Availability unrestricted Abstract
It is well known that the costs associated with drug discovery are extremely high due the use of expensive in vitro methods as well as the high failure rate of drugs during clinical testing. In order to effectively fight the war against diseases such as malaria a far less expensive approach is required. Increasing the amount of in silicoIn silico methods have the ability to predict major limiting factors in drug discovery resulting in only high quality drug molecules being subjected to clinical trials, thus increasing the probability of success.
In this study a web-based chemoinformatics workspace aimed at research biologists was developed inside the FunGIMS application framework. This particular web-based chemoinformatics application was developed in the context of the FunGIMS suite of tools, specifically providing biological users with some of the most common chemoinformatics functions such as (1) the representation of chemical compounds, (2) chemical data, (3) databases and data sources, (4) structure search methods, (5) methods for calculating physical and chemical data (6) calculation of structure descriptors. The chemoinformatics module is supported by a modified version of the CHEBI database and the integration of OpenBabel and Frowns made it possible to perform analysis on molecules by means of SMILES-structures.
As part of the validation of the chemoinformatics module of FunGIMS, the chemical space of the polyamine pathways in Plasmodium was explored in order to obtain a library of molecules based on similarities that could be possible lead-like compounds. This was used in a study of compounds against spermidine synthase from Plasmodium falciparum. By means of similarity and substructure searches the chemoinformatics module was able to produce molecules that are structurally similar. Additional filtering enabled a library of related molecules to be obtained, and used in a docking study. Compounds were found with high docking scores, thereby validating the effectiveness and usefulness of the chemoinformatics module of FunGIMS.Copyright © 2008, 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:
De Bruin, JJ 2008, Discovery and characterization of polyamine analogues as inhibitors of the Plasmodium falciparum polyamine pathway using cheminformatics, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-08112009-141406/ >E1361/gm
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