Title : Increasing of secondary metabolites against malaria by mutagenesis
Abstract:
Malaria is one of the most important health problems in tropical and subtropical regions. The estimated clinical cases for WHO were 216 million in 2010, approximately disease, mainly children under 5. A major obstacle to malaria control is the emergency and spread of antimalarial resistance drugs, and urgent efforts are necessary to identify new classes of antimalarial drugs.
Plants produce more than thousands of different compounds through the secondary metabolism pathways. Secondary metabolites are often the keystone in the interactions between plants and their environment. The properties of these molecules are used in traditional medicine (80% of the World’s population, especially in the developing world), but also in modern allopathic medicine through the use of purified or derived components obtained from chemical hemi-synthesis. Plants have been used medicinally throughout history, and the two best conventional antimalarial drugs, artemisinin from Artemisia annua and quinine from Cinchona sp, are both derived from traditional medicines.
Phyllanthus odontadenius is present in all the coastal countries of West Africa to southern Africa. In Rwanda, the stem part extract is used to treat diarrhea and cholera. The alcohol crude extracts of leaves and stems have used to calm diarrhea induced castor oil in mice. It has been widely used in treating a number of traditional ailments and has demonstrated in vitro antibacterial actions against some bacteria, as well as in vivo and in vitro anti-malaria properties.
Metabolic engineering approach is one of pathways in the production of secondary metabolites with economic interest value. To that, metabolic engineering approach consists to modify the plant physiology to make it produce a molecule of economic interest. Experimentally, induced mutations provide an important source for variability. It is known that various chemicals have several effects on living organisms. Chemical mutagen generally produce induced mutations which lead to base pair substitution especially GC:AT resulting in aminoacid changes, which change the function of proteins but do not abolish their functions as deletions or frame shift mutations mostly. These chemomutagens induce a broad variation of morphological and yield structure parameters in comparison to normal plants.
Sodium azide (NaN3) is a mutagen and it has proved to be one of the most powerful mutagens in crop plants. It is a common bactericide, pesticide and industrial nitrogen gas generator if known to be highly mutagenic in several organisms, including plants and animals. In order to understand that NaN3 is mutagenic mechanism used for the improvement economic characters to many studies in crop plants.
In our works, NaN3 was used as mutagen for increasing secondary metabolites with antimalarial effects in P. odontadenius aerial parts.
Results obtained on antimalarial activities showed that the best activities were 1.09±0.13 µg/ml (5 mM of NaN3) to 1.04 ±0.02 µg/ml (10 mM of NaN3) at the first generation (M1) and 3.26±0.05 µg/ml (7.5 Mm of NaN3) to 4.52±0.12 µg/ml (10 mM of NaN3) at the second generation (M2). These results coincided with the chemo-sensitivity of NaN3 on seeds germination (LD30 = 4.76 mM and LD50 = 10.99 mM).
This work will be continuous for the stabilization of plant mutated and the characterization of plant mutations.
