Embed Size (px)
Citation preview
The potential of plants as a source of anti-malarial agents
Dr Geoffrey M. RukungaKenya Medical Research InstitutePO BOX 54840NAIROBIE-mail <[email protected]>
Global statistics of Malaria
1.5 – 2.7 million deaths annually
Over 1 billion clinical episodes
300 – 500 million people infected
Every 10 – 30 seconds a child dies of malaria
Impact of malaria in Africa
Major health problem in the tropics
About 90 million clinical cases annually.
Malaria leads to economic loss.
Most affected are pregnant women and children
Under 5 years.
What contributes to the problem?
Resistance to conventional drugs.
Affordability of available drugs.
There for need to continue searching for new agents
Plant drugs
Approximately 80% of the people in the developing countries depend on traditional medicine.
The discovery of quinine and artemisinin has stimulated interest in medicinal plants as sources of new antimalarial drugs.
Selection of plants for antimalarial activity
Ethno medical bases
Random selection
Methodologies
Extractions – water or organic solvent In vitro assays – IC 50s Cytotoxicity assays CC50’s Selectivity index (S.I) = IC 50/CC50 In vivo assays – percentage chemosuppression of parasitaemia. Toxicity in animals. Activity guided isolation of the active compound (?)
So many publications yet few candidates anti-malarial agents
Anti-malarial compounds rare.
Most studies ends up with only in vitro assays.
If beyond in vitro assay – then toxicity - problem
Usually because of lack of resources- trained personnel- equipment- Finances
Categorization of plants extracts with in vitro anti-plasmodial activity
Category 1: High activity IC 50 equal or less than 10 g/mL Category 2: Moderate activity IC 50 between 10 and 100 g/mL Category 3: Low or no activity IC 50 Above 100 g/mL
Category 1 (High activities)
120 plant extracts from 74 plant species, belonging to 34 families.Some of the families with more species than others:Annonaceae (alkaloids) Apocynaceae (Alkaloids)Asteracea (sesquiterpenes) Celestraceae (Triterpenes)Meliaceae (limonoids) Simaroubaceae (quassinoids)Menispermaceae (Alkaloids) Rutaceae (Alkaloids)Rubiaceae (alkaloids)
Category 2 – moderate activities
203 plant extracts from 129 plant species, belonging to 50 families.Some of the families with more species than others:
Annonaceae Asteraceae Meliaceae Loganiacea Fabaceae
Classes of compounds with high anti-malarial activities
Alkaloids Basic compounds -highly bioactive compounds.
The structures are very diverse
Families containing the compounds includesAnnonaceae LoganiaceaeMenispermaceae AsclepiadaceaeDioncophyllaceae RubiaceaRutaceae Apocynaceae
Quinine – An alkaloidal compound
5
N
HOH
NH
H
CH2
CH3O
Quassinoids
Heavily oxygenated lactones majority with C-20 basic skeleton.
The structures are very diverse
Simaroubaceae – is the family associated with quassinoids
A quassinoid from Simaba guianensis (Simaroubaceae)
IC 50 < 1.7 ng/mL
Sesquiterpenes
Biosynthetically made from three 5-carbon isoprene units skeleton Among the most active terpenoids Artemisinin belongs to thisd class of compounds. Families identified with highly active sesquiterpenes includesAsteraceae SiparunaceaeCyperaceae ValerianaceaeRosaceae
Artemisinin and Mustakone
O
O
O
O
H
CH3
CH3
H
H3C
H
O
1
2
3
45
6
7
8910
11
12
13
14
15
O
Triterpenes
Triterpenes. Biosynthetically made from 6 units isoprene units Diverse sructures.Some triterpenes have exhibited high anti-plasmodial activity.Families associated includes:-Ancistrocladaceae- Meliaceae- Simaroubaceae- Celestraceae
pristimerin – triterpene from Maytenus senegalensis - Celestraceae
Me
MeMe
Me
HO
O
Me
CO2MeMe
IC 50 < 200 ng/mL
Limonoids
Tetranoterpenoids a class of compounds highly active.
O
O
O
O
O
OAc
O
OCOOCH3
OO
O
IC 50s < 1ug/mL
Family associated with these compounds – Meliaceae
Discussions
Points to consider in the categorization of the plant extracts with anti-plasmodial activity.
Type of extract Strain of Plasmodium parasite used in the assay Part of the plant extracted Geographical location of plant Time of the year harvested Thus categorization is a guide
Way forward
Prioritization of plants as source of anti-malarial agents. Families whose exts have high anti-malarial activity (cat 1&2). Families that contain class of compounds with known potent anti-malarial activity e.g liminoids, alkaloids, quassinoids etc. Cytotoxicity after in vitro anti-plasmodial assays. Confirm activity in vivo Toxicity studies in animals. plant part: leaves > stems > roots Ease of propagation, cultivation etc Team work – the only answer.
End
Thank you
