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The potential of plants as a source of anti-malarial agents Dr Geoffrey M. Rukunga Kenya Medical Research Institute PO PowerPoint Presentation
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The potential of plants as a source of anti-malarial agents Dr Geoffrey M. Rukunga Kenya Medical Research Institute PO BOX 54840 NAIROBI E-mail <grukunga@kemri.org>. Global statistics of Malaria. 1.5 – 2.7 million deaths annually Over 1 billion clinical episodes

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slide1

The potential of plants as a source of

anti-malarial agents

Dr Geoffrey M. Rukunga

Kenya Medical Research Institute

PO BOX 54840

NAIROBI

E-mail <grukunga@kemri.org>

global statistics of malaria
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
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
What contributes to the problem?
  • Resistance to conventional drugs.
  • Affordability of available drugs.

There for need to continue searching

for new agents

plant drugs
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
Selection of plants for antimalarial activity
  • Ethno medical bases
  • Random selection
methodologies
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
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
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
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
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
Classes of compounds with high anti-malarial activities
  • Alkaloids
  • Basic compounds -highly bioactive compounds.
  • The structures are very diverse
  • Families containing the compounds includes

Annonaceae Loganiaceae

Menispermaceae Asclepiadaceae

Dioncophyllaceae Rubiacea

Rutaceae Apocynaceae

quassinoids
Quassinoids
  • Heavily oxygenated lactones majority with

C-20 basic skeleton.

  • The structures are very diverse
  • Simaroubaceae – is the family associated with

quassinoids

sesquiterpenes
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

includes

  • Asteraceae Siparunaceae
  • Cyperaceae Valerianaceae
  • Rosaceae
triterpenes
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
limonoids
Limonoids

Tetranoterpenoids a class of compounds highly active.

Family associated with these compounds – Meliaceae

IC 50s < 1ug/mL

discussions
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
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.
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End

Thank you