Plasmodium falciparum: effect of Solanum nudum steroids on thiol contents and beta-hematin formation in parasitized erythrocytes.
We studied the effects on total thiols glutathione (GSH) and cysteine contents in Plasmodium falciparum in vitro when treated with four steroid derivatives and a sapogenin (Diosgenone) extracted from Solanum nudum. We also determined their capacity to inhibit beta-hematin formation. We showed that SN-1 (16alpha-acetoxy-26-hydroxycholest-4-ene-3,22-dione) increased total glutathione and cysteine concentrations while SN-4 (26-O-beta-d-glucopyranosyloxy-16alpha-acetoxycholest-4-ene-3,22-dione) decreased the concentration of both thiols. Acetylation in C16 was crucial for the effect of SN-1 while type furostanol and terminal glucosidation were necessary for the inhibitory properties of SN-4. The combination of steroids and buthionine sulfoximine, a specific inhibitor of a step-limiting enzyme in GSH synthesis, did not modify the glutathione contents. Finally, we found that SN-1 inhibited more than 80% of beta-hematin formation at 5.0mM, while the other steroids did not show any effect.
Grupo Malaria, Universidad de Antioquia, Medellín, Colombia. Apabon72@gmail.com
Adriana
A
Pabón
Eric
E
Deharo
Lina
L
Zuluaga
Juan D
JD
Maya
Jairo
J
Saez
Silvia
S
Blair
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003545:Cysteine / Q000032:analysis / Q000187:drug effects; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects / Q000469:parasitology*; D005978:Glutathione / Q000032:analysis / Q000187:drug effects; D006420:Hemeproteins / Q000096:biosynthesis* / Q000187:drug effects; D016014:Linear Models; D016778:Malaria, Falciparum / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects*; D032322:Solanum / Q000737:chemistry*; D013141:Spiro Compounds / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology* / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology
D006420:Hemeproteins; D010936:Plant Extracts; D013141:Spiro Compounds; D013256:Steroids; D013438:Sulfhydryl Compounds; D014315:Triterpenes; C469690:diosgenone; C020753:hemozoin; D019328:Buthionine Sulfoximine; D005978:Glutathione; D003545:Cysteine