Trypanocidal activity of a nitrovinylfuran derivative (SQ 18,506) in mice

In search of anti-Trypanosoma cruzi drugs: new leads from a mouse model

“…The triphenylmethane derivative, TAC pamoate, is known to have antischistosomal effects13 and activity against African trypanosomes.14,15 Here, it was found to be active in the T. cruzi mouse model, but it was less effective than nifurtimox. The activity observed for the nitrofuran compound 12 was not unexpected since the nitrofurans have activity against T. cruzi2,3,6 as well as other microorganisms (e.g., see ref [16][17][18][19][20]. Since completion of our testing the trons-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-l,2,4-oxadiazole, there have been preliminary reports21,22 that this compound has been effective in therapy of acute experimental T. cruzi infections at levels comparable with nifurtimox (compound 1).…”

The biochemistry of African trypanosomes and its significance for chemotherapy

“…In fact, the drug dipyridamol, a known inhibitor of adenosine and thymine uptake in mammalian cells, has also been shown to inhibit adenosine uptake in T. brucei and T . congohe; but the comparatively high concentrations required for this action make unlikely the applicability of this compound as a trypanocidal agent for routine clinical use (James 8c Born, 1980). Indeed, earlier studies had shown that a synthetic adenine nucleoside, 5'-O-sulfamoyl adenosine (Jaffe et al, 1971) and a nitrovinylfuran derivative (Jaffe & Meymerian, 1973) had trypanocidal properties, presumably due to their competitive inhibition of trypanosomal uptake of native purines.…”

“…congohe; but the comparatively high concentrations required for this action make unlikely the applicability of this compound as a trypanocidal agent for routine clinical use (James 8c Born, 1980). Indeed, earlier studies had shown that a synthetic adenine nucleoside, 5'-O-sulfamoyl adenosine (Jaffe et al, 1971) and a nitrovinylfuran derivative (Jaffe & Meymerian, 1973) had trypanocidal properties, presumably due to their competitive inhibition of trypanosomal uptake of native purines. Certain purine analogues, the pyrazolopyrimidines such as allopurinol and thiopurinol, their respective ribonucliosides, and the C-nucleosides formycin B and 9-deazainosine, have been studied in T. h e i gambic7lse and T. h e i rhodesiense, in vitro.…”