Global statistics of Malaria

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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 ltgrukunga_at_kemri.orggt
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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

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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.

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What contributes to the problem?

• Resistance to conventional drugs.
• Affordability of available drugs.
• There for need to continue searching
• for new agents

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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.

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Selection of plants for antimalarial activity

• Ethno medical bases
• Random selection

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Methodologies

• Extractions water or organic solvent
• In vitro assays IC 50s
• Cytotoxicity assays CC50s
• Selectivity index (S.I) IC 50/CC50
• In vivo assays percentage chemosuppression
• of parasitaemia.
• Toxicity in animals.
• Activity guided isolation of the active compound
  (?)

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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

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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

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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) Asterac
ea (sesquiterpenes) Celestraceae
(Triterpenes) Meliaceae (limonoids)
Simaroubaceae (quassinoids) Menispermaceae
(Alkaloids) Rutaceae (Alkaloids) Rubiaceae
(alkaloids)
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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
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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

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Quinine An alkaloidal compound
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Quassinoids

• Heavily oxygenated lactones majority with
• C-20 basic skeleton.
• The structures are very diverse
• Simaroubaceae is the family associated with
• quassinoids

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A quassinoid from Simaba guianensis
(Simaroubaceae)
IC 50 lt 1.7 ng/mL
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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

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Artemisinin and Mustakone
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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

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pristimerin triterpene from Maytenus
senegalensis - Celestraceae
IC 50 lt 200 ng/mL
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Limonoids
Tetranoterpenoids a class of compounds highly
active.
Family associated with these compounds
Meliaceae
IC 50s lt 1ug/mL
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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

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Way forward

• Prioritization of plants as source of
• anti-malarial agents.
• Families whose exts have high anti-malarial
  activity (cat 12).
• 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 gt stems gt roots
• Ease of propagation, cultivation etc
• Team work the only answer.

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End Thank you