Aminoquinolone WR6026 as a feasible substitute for gentian violet in Chagas' disease prophylaxis in preserved blood for transfusional purposes

Abstract

The search for a colorless, nontoxic and efficient drug to prevent transfusion-associated Chagas' disease (TACD) has been underway unsuccessfully since 1953 when gentian violet was preconized and to date is still being used as the only in vitro trypanocidal agent. The recent findings of aminoquinolone "WR6026" as a trypanocidal agent, led the authors to study the metabolism of red cells stored with this compound, the main objective of which was to define its applicability in TACD control. Ten units of human whole blood collected in CPDA-1 were divided into two equal satellite bags. One had "WR6026" (final concentration 62.5µg/mL) added and the other was used as a control, both were stored at 4ºC. At baseline, day 7, 14, 21 and 28, samples were taken for the following measurements: adenosine triphosphate (ATP), hemoglobin, electrolytes (sodium and potassium), gases (pO2 and pCO2) and osmotic fragility. The results of tests and control were analyzed through parametric t-student test. The results were similar in both groups throughout the experiment except for the level of ATP on day 14, which presented significantly higher values in the tests when compared with the controls (p = 0.012). It was concluded that WR6026 does not interfere in the preservation and probably the viability of the erythrocytes also until day 28 of storage. Consequently the authors suggest that WR6026 could emerge as a colorless substitute for gentian violet in the control of TACD in endemic areas.

Synthesis and trypanocidal activity of ent-kaurane glycosides

“…2 An 8-aminoquinoline compound (WR6026) seems to be the most promising candidate to prevent transfusion associated Chagas' disease. 6,7 The in vitro assay with T. cruzi trypomastigotes could also lead to the identification of potential drugs for Chagas' disease chemotherapy. The in vitro active compounds should be further evaluated for in vivo sensitivity in mice experimentally infected with T. cruzi.…”

Trypanocidal Activity of Triterpenes from Arrabidaea triplinervia and Derivatives

“…3,8) As far as we are aware, the most promising candidate for Chagas' disease prophylaxis is a hydrosoluble aminoquinoline [6-methoxy-8-(diethylamino)lepidine dihydrochloride, WR6026], which was effective for clearance of parasites from infected blood at doses comparable to gentian blue (65, 135 mg/ml). 13,21) …”

In vitro Activities of Pfaffia glomerata Root Extract, Its Hydrolyzed Fractions and Pfaffic Acid Against Trypanosoma cruzi Trypomastigotes

“…To date, gentian violet is the only compound that can eliminate the parasite in blood prior to transfusion. Despite its efficacy, there are several restrictions on the use of this compound . The drugs Nifurtimox (Nf) and benznidazole are currently available to treat chagasic patients.…”