Antimalarial Activity Of Glycoalkaloids In Vivo

Malaria is still one of the major health problems in the world. Multi-drug resistance is oneof the most important problems in malaria control over the years. Recent years, the situationworsened with the emergence of chloroquine-resistant Plasmodium falciparum, and theirspread has stimulated the development of new effective treatments against malaria .Glycoalkaloids(GAS) are important natural products which are mainly existed in someplants of the Solanaceae and the Liliaceae. Plants produce glycoalkaloids in order to protectthemselves from the attack from virus, microbial, fungus, insects and animals. Previousstudies have shown that the glycoalkaloid from Solanum is used in folk medicine for thetreatment of disease. Recently, tomatine was describe, a glycoalkaloid based adjuvant,capable of stimulating potent antigen-specific humoral and cellular immune responses thatcontribute to protection against malaria.The present work was antimalarial activity of glycoalkaloids on Swiss ICR mice in vivo. Inthis work, the aim was to identify the structure activity relationship of glycoalkaloids. First,we tested the activities of extracted glycoalkaloids. By modifying the structure ofglycoalkaloids if can be estimated what roles the sugar chains of glycoalkaloids play in theantimalarial activities. The results of this thesis as follow:1. The chaconine was highly antimalarial activity (ED50=4.49mg/kg).2. These five glycoalkaloids are α-chaconine,α-solanine,tomatine,solasonine andsolamagine. The carbohydrate moiety of five glycoalkaloids is the major formation of theantimalarial activity. The antimalarial activity of chacotriose on chaconine and solamargine isstronger than the solatriose on solanine and solasonine. the antimalarial activity oflycotetraose in tomatine was obvious stronger than other trisaccharide in glycoalkaloids. Thetridimensional construction of trisaccharide and tetrasaccharide are different, so there are otherreasons related to the antimalarial activity of glycoalkaloids, such as construction.3. The present work showed the the 6-hydroxy groups of D-glucose of chaconine is themajor active location, because the 6-O-sulfated-chaconine is obvious antimalarial inactivity.4. The mixture of α-chaconine and α-solanine is weaker than the active addition ofα-chaconine and α-solanine. The result indicated interaction of α-chaconine and α-solanine isantagonism.