title: Plasmodium berghei: in vitro and in vivo activity of dequalinium.
abstract: 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.
authors.affiliation: Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, Caracas 1051-A, Venezuela. rodriguh@ucv.ve
authors.forename: Juan Ricardo
authors.initials: JR
authors.lastname: Rodrigues
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa de Domínguez
mesh_terms: 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
chemical_list: D000890:Anti-Infective Agents; D006420:Hemeproteins; C020753:hemozoin; D005914:Globins; D003868:Dequalinium