In vivo antimalarial activities of glycoalkaloids isolated from Solanaceae plants.
BACKGROUND
Malaria is one of the most common and serious protozoan tropical diseases. Multi-drug resistance remains pervasive, necessitating the continuous development of new antimalarial agents.


OBJECTIVE
Many glycosides, such as triterpenoid saponins, were shown to have antimalarial activity against Plasmodium falciparum in vitro. This study was to elucidate the ability of five glycoalkaloids against Plasmodium yoelii and develop new antimalarial lead compounds.


METHODS
Glycoalkaloids were isolated from three kinds of Solanaceae plants: chaconine and solanine were isolated from Solanum tuberosum L. sprouts, solamargine and solasonine from Solanum nigrum L. fruit, tomatine from Lycopersicon esculentum Mill. fruit. The five isolated glycoalkaloids were evaluated against Plasmodium yoelii 17XL in mice with 4-day parasitemia suppression test in different concentrations.


RESULTS
Chaconine showed a dose-dependent suppression of malaria infection, ED50, 4.49 mg/kg; therapeutic index (TI), approximately 9. At a dose of 7.50 mg/kg, the parasitemia suppressions of chaconine, tomatine, solamargine, solasonine and solanine were 71.38, 65.25, 64.89, 57.47 and 41.30%, respectively. At 3.75 mg/kg, the parasitemia suppression of chaconine was 42.66%, but the derivative, chaconine-6-O-sulfate, appeared to show no antimalarial activity. Simultaneous administration of chaconine and solanine in 1:1 did not show any synergistic effects.


CONCLUSIONS
The results showed that the glycoalkaloids with chacotriose (chaconine and solamargine) were more active than those with solatriose (solanine and solasonine). Chaconine was the most active among the five glycoalkaloids. We propose that the activity is dependent upon non-specific carbohydrate interactions. The 6-OH of chaconine is important for antimalarial activity.
Chen
Yan
Y
School of Life Sciences, Northeast Normal University, Changchun 130024, China.
Li
Shengyu
S
Sun
Fang
F
Han
Han
H
Zhang
Xu
X
Fan
Yuying
Y
Tai
Guihua
G
Zhou
Yifa
Y
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005260:Female; D006027:Glycosides / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D007928:Lethal Dose 50; D018551:Solanum lycopersicum / Q000737:chemistry; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D018512:Parasitemia / Q000188:drug therapy; D010967:Plasmodium yoelii / Q000187:drug effects*; D019657:Solanaceae / Q000737:chemistry*; D012991:Solanaceous Alkaloids / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D032324:Solanum nigrum / Q000737:chemistry; D011198:Solanum tuberosum / Q000737:chemistry; D013329:Structure-Activity Relationship
D000962:Antimalarials; D006027:Glycosides; D012991:Solanaceous Alkaloids