Project topics and materials
Get Complete Project Material File(s) Now! »
Triterpenes
Triterpenes are C30 compounds arising from the cyclization of squalene. They are comprised of a variety of structurally diverse compounds, which include steroids. Tetracyclic terpenes and steroids have similar structures but have different biosynthetic pathways (Taiz and Zeiger, 2006).
Steroids contain a ring system of three six-membered and one five-membered ring. Because of the profound biological activities encountered, many natural steroids together with a considerable number of synthetic and semi-synthetic steroidal compounds, are employed in medicine (e.g. steroidal saponins, cardioactive glycosides, corticosteroid hormones and mammalian sex hormones). The pharmaceutical applications of triterpenes and steroids are considerable (Gurib-Fakim, 2006).
Phenolic compounds
All phenolic compounds have an aromatic ring that contains various attached substituent groups such as hydroxyl, and methoxy (-O-CH3) groups, and often other non-aromatic ring structures. They range from simple structures with one aromatic ring to complex polymers such as tannins and lignins. Phenolics differ from lipids in being more soluble in water and less soluble in non-polar organic solvents. Some phenolics, however, are rather soluble in ether, especially when the pH is low enough to prevent ionization of any carboxyl and hydroxyl group present. These properties greatly aid separation of phenolics from one another and from other compounds (Taiz and Zeiger, 2006). Other classes of phenolic compounds include coumarines, quinones and flavonoids.
Phenolic compounds are synthesised via the Shikimic acid or acetate pathway (Fig 1.5) and subsequent reactions. They have a wide range of pharmaceutical activities such as anti-inflammatory, analgesic, antitumour, anti-HIV, anti-infective (antidiarrhoeal, antifungal), antihepatotoxic, antilipolytic, antioxidant, vasodilatory, immunostimulant and antiulcerogenic. In plants they serve as effective defence against herbivores (Wink, 1999 and Gurib-Fakim, 2006).
Malaria
Malaria is a protozoal disease caused by parasitic protozoa of the genus Plasmodium. It is transmitted to humans by the female Anopheles mosquito.
There are over three hundred species of Anopheles mosquito, however, only about sixty are able to transmit the malaria parasite. Malaria commonly affects the populations of tropical and subtropical areas world wide, as well as increasing number of travellers to and from these areas. The following four species of Plasmodium cause the disease in its various forms: P. falciparum, P. vivax, P. ovale and P. malariae. P. falciparum is the most widespread and dangerous of the four as it can lead to the fatal cerebral malaria, which often results in death (Hyde, 2002). Today some 500 million people in Africa, India, South East Asia and South America are exposed to endemic malaria and it is estimated to cause 2.5 million deaths annually, one million of which are children. Although malaria is found in over 100 countries (Fig. 1.8 and 1.9), the major burden of the disease is carried by the nations of Africa, where over 90% of all falciparum malaria deaths are recorded, and where the high levels of morbidity and transmission place considerable strain on public health services and economic infrastructure (Hyde, 2002). In the absence of effective vaccines, management of the disease has depended largely upon chemotherapy and chemoprophylaxis. Of the various antimalaria drugs available, the aminoquinoline, chloroquine was for several decades the agent of choice, as it was safe, effective and cheap. Parasite resistance to this drug was first observed in Thailand in 1957 and then on the border of Colombia and Venezuela in 1959. By the late 1970s it had spread to East Africa and by the mid-1980s had become a major problem in several areas in Africa (Wernsdorfer and Payne, 1991). Although the increasing prevalence of drug resistant P. falciparum has hindered the ability to control/treat the disease, it has at the same time intensified attempts to develop novel antimalaria drugs and agents to prolong chloroquine. The most widely used combination of this type consist of pyrimethamine (PYR) and sulfadoxine (SDX), known as fansider or SP, which is cheap and, until recently, was effective against the chloroquine-resistant parasites found in Africa. However, resistance to this formulation, long established in parts of south-east Asia and South America (Wernsdorfer, 1994), now threatens to leave Africa with no affordable treatment. Further combinations of antifolates with newer drugs such as the artemisinin derivatives, or the development of alternative combinations, may be the only way to limit the pace of the parasitic resistance to chemotherapy. For example, the antifolate prodrug, proguanil, has now been formulated together with a new type inhibitor, atovaquone, to yield malarone, recently licensed for clinical use (Hyde, 2002).
Developing countries, were malaria is epidemic, still depend on traditional medicine for the treatment of the disease. However, little scientific data are available to assess the efficacy of these herbal remedies. On the other hand, it is accepted that the recognition and validation of traditional medicinal practices could lead to new plant derived drugs, e.g. artemisinin from Artemisia annua, a Chinese traditional medicine plant (Ridley, 2002).
Therefore it is important that medicinal plants which have a folklore reputation for antimalarial properties are investigated, in order to establish their efficacy and to determine their potential as a source of new antimalarial drugs (Tran et.al., 2003). South Africa is an ideal place to search for a new drug because of its remarkable biodiversity and rich cultural traditions of plant uses.
Chapter 1: Introduction
1.1 Medicinal plants
1.2 Traditional medicine
1.3 Drug discovery from medicinal plants
1.4 Synthesis and role of plant secondary metabolites
1.5 Infectious diseases
1.6 Antioxidant activity
1.7 Croton steenkampianus
1.8 Objectives
1.9 Scope of the thesis
1.10 Hypothesis
1.11 References
Chapter 2: Bioassay guided fractionation of the crude extract from Croton steenkampianus
2.1 Introduction
2.2 Materials and Methods
2.3 Results and Discussion
2.4 References
Chapter 3: Antiplasmodial bioactivity of crude extract and isolated compounds
3.1 Introduction
3.2 Methods
3.3 Results and Discussion
3.4 References
4.1 Introduction
4.2 Materials and Methods
4.3 Results and Discussion
4.4 References
5.1 Introduction
5.2 Materials and Method
5.3 Results
5.4 Discussion
5.5 References
6.1 Introduction
6.2 Materials and Method
6.3 Results and Discussion
6.4 References
7.1 Introduction
7.2 Bioassay guided fractionation of the ethanol crude extract and isolated compounds
7.3 Biological evaluation of the isolated compounds
7.4 References
