RASOANAIVO Malagashanine

Malagashanine:
From traditional knowledge
to clinical trials
Philippe Rasoanaivo
Institut Malgache de Recherches Appliquées

SUMMARY
1- Basic background of resistance
2- Strategies to overcome drug resistance
3- Contribution of a traditional recipe in the
treatment of chloroquine resistant malaria
4- Mechanisms of chloroquine resistance

LIVING ORGANISMS
Reproductive system

BIRTH

DEATH

RESISTANCE

Bacterias, Fungi,
Parasites,Viruses,

Infectious diseases
Cancerous
Cells

Drug resistance
Vector resistance

World malaria situation

Areas where drug-resistant malaria
has been reported

World malaria situation
Resistance to Chloroquine
Resistance to Fansidar
Multi-drug resistance

Strategies to overcome drug resistance

NEW DRUGS
Drug combination
Truly innovative
Imitative
Resistance modulators

Strychnos diplotricha
Strychnos myrtoides

Strychnos mostueoides

Hazomalania voyroni

Strychnopsis thouarsii
Spirospermum penduliflorum
Burasaia madagascarienis

Preliminary investigation of Strychnos species
1.00

50
0.80

In vitro

45

In vivo

40
35

0.60

30
25
0.40

20
15
10

0.20

5
0

0.00
0.00

0.20

0.40

0.60

0.80

1

1.00

N

2

CH3
H

N
Ac

CO2CH3
H
O

Malagashanine

3

4

Traditional recipe

Clinical trials

Clinical observation
Pre-clinical investigations
Phytochemistry
Pharmacology
Toxicology
Pharmacokinetics

Opened clinical trials

Randomised, double blind
Clinical trial

Ankazobe

Resistance

Host

Pacific cohabitation ?

Drugs

Invading organism

Mechanism of chloroquine resistance and its reversal:
The 1,4-diamino hypothesis
Me
N

O
CH3

N
N
H

O

N

CH3

O

Strychnobrasiline

CH3

Spermostrychnine

HN
Me

Cl

Me
N

CO2Me

N
H

N
H

O

Malagashanine

N
N

N

Chloroquine
N

N
Cl

Chlorpheniramine

MeO
MeO

CN Me
N

Verapamil

R
OMe
OMe

synthetic chemosensitiser

MDR Resistance

OCH3

H3CO

OCH3
CH3
N
O
O
OCH3
OCH3

O
O

Pervilleine D

OCH3

Thank you for your attention