Title page for ETD etd-04162007-102438

Document Type Master's Dissertation
Author Pillay, Pamisha
Email ppillay@csir.co.za
URN etd-04162007-102438
Document Title Structure elucidation of antiplasmodial sesquiterpene lactones from Vernonia staehelinoides and Oncosiphon piluliferum
Degree MSc (Chemistry)
Department Chemistry
Advisor Name Title
Prof R Vleggaar
  • Medicinal plants
  • Materia medica
  • Sesquiterpene lactones
  • Vegetable
  • Malaria Treatment
Date 2006-09-07
Availability unrestricted

Malaria continues to be a major cause of mortality and morbidity especially in Sub-Saharan Africa. The emergence and spread of drug resistant parasites has highlighted the need for new chemically diverse, effective drugs. Historically, one of the major sources of antimalarial agents and novel template compounds has been higher order plants. The widespread use of medicinal plants for the treatment of malaria in South Africa represents a diverse resource of potential antimalarial drugs.

Two South African plants, Vernonia staehelinoides and Oncosiphon piluliferum, were identified as potential sources of new antimalarial drugs through a national multidisciplinary-consortium project aimed at scientifically validating South African medicinal plants for the treatment of malaria. The in vitro antiplasmodial activity of extracts of these plants warranted further investigation to identify the biologically active components. Bio-assay guided fractionation based on in vitro antiplasmodial activity against the D10 P. falciparum strain was used to identify the compounds responsible for the observed activity. Compounds were purified using silica gel column chromatography. The structures of the isolated compounds were elucidated using spectroscopic techniques.

Bioassay-guided fractionation of the organic extracts of V. staehelinoides leaves identified a pair of structurally-related hirsutinolides with significant in vitro antiplasmodial activity. The compounds were found to be cytotoxic at similar concentrations but proved to be interesting scaffolds for potential structure-activity relationship studies.

Three germacranolides and two eudesmanolides were identified through bioassay-guided fractionation of the organic O. piluliferum extract. Selected derivatizations were conducted in order to fully characterize the compounds. The absolute configuration of the major active germacranolide was determined using Mosher's method. The effect of the reduction of the a-methylene group of the major active germacranolide on antiplasmodial activity and cytotoxicity was also investigated. The 5 compounds and the reduction product were found to possess varying degrees of in vitro antiplasmodial activity and cytotoxicity. None was sufficiently active or selective to be a viable drug candidate but the potential for further structure-activity relationship studies exists.

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  00front.pdf 166.07 Kb 00:00:46 00:00:23 00:00:20 00:00:10 < 00:00:01
  01chapter1.pdf 241.02 Kb 00:01:06 00:00:34 00:00:30 00:00:15 00:00:01
  02chapter2.pdf 103.60 Kb 00:00:28 00:00:14 00:00:12 00:00:06 < 00:00:01
  03chapter3.pdf 384.95 Kb 00:01:46 00:00:54 00:00:48 00:00:24 00:00:02
  04chapter4.pdf 934.56 Kb 00:04:19 00:02:13 00:01:56 00:00:58 00:00:04
  05chapter5.pdf 226.41 Kb 00:01:02 00:00:32 00:00:28 00:00:14 00:00:01
  06appendices.pdf 153.41 Kb 00:00:42 00:00:21 00:00:19 00:00:09 < 00:00:01

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