Plasmodium berghei: in vitro and in vivo activity of dequalinium.
Bisquinoline compounds have exhibited remarkable activity in vitro and in vivo against Plasmodium parasites by inhibition of heme detoxification. We have tested the ability of dequalinium 1,1'-(1,10-decanediyl)bis(4-amino-2-methylquinoline), a known antimicrobial agent, to inhibit beta-hematin synthesis using a non-emzymatic colorimetric assay and globin proteolysis by electrophoretic analysis (SDS-PAGE-15%). Dequalinium was able to inhibit both processes in vitro with close correlation to a murine malaria model, reducing parasitemia levels, prolonging the survival time post-infection and curing 40% of infected mice using a combination therapy with a loading dose of chloroquine. These results confirm that dequalinium is a promising lead for antimalarial drug development.
Rodrigues
Juan Ricardo
JR
Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, Caracas 1051-A, Venezuela. rodriguh@ucv.ve
Gamboa de Domínguez
Neira
N
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003124:Colorimetry; D003868:Dequalinium / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005914:Globins / Q000187:drug effects / Q000378:metabolism; D006420:Hemeproteins / Q000096:biosynthesis / Q000187:drug effects; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D010962:Plasmodium berghei / Q000187:drug effects* / Q000378:metabolism
D000890:Anti-Infective Agents; D006420:Hemeproteins; C020753:hemozoin; D005914:Globins; D003868:Dequalinium