In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi.
The toxic effect of lapachol, beta-lapachone and several 1,2-naphthoquinone derivatives on the growth, viability and infectivity of Trypanosoma cruzi were compared. beta-lapachone was the most active compound in vitro. No inhibition was observed in suspensions which contained inactivated foetal calf serum or rabbit haemoglobin solution. The infectivity of trypomastigotes in mice was not affected when cells were previously incubated with beta-lapachone or one of several other naphthoquinone derivatives in vitro in the presence of blood. It is suggested that beta-lapachone and the other compounds can be inactivated either by reduction in the presence of oxyhaemoglobin or by interaction with serum proteins. A beta-lapachone derivative, allyl-beta-lapachone, was not inactivated in the presence of blood and remained effective in suppressing trypomastigote infectivity.
D000818:Animals; D001769:Blood / Q000469:parasitology; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D008706:Methemoglobin; D051379:Mice; D009068:Movement / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D010108:Oxyhemoglobins; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity
D009285:Naphthoquinones; D010108:Oxyhemoglobins; C014638:beta-lapachone; D008706:Methemoglobin