ABSTRACT
The antischistosomal and antitrypanosomal drug trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole [(SQ18506) CAS: 28754-68-9; (E)-amino-3-(2-(5-nitro-2-furyl)-vinyl)-1,2,4-oxadiazole] was carcinogenic for both male and female CD-1 mice when it was administered either in the diet or by gastric intubation. Dose-dependent increases in tumors of the forestomach and lymphatic tissues were observed in all groups receiving SQ18506 including mice infected with Schistosoma mansoni. The predominant tumor observed was squamous cell carcinoma of the forestomach. The presence or absence of schistosome infection did not appear to alter the incidence or distribution of tumors at comparable doses of SQ18506. The incidence of bladder tumors was positively correlated with the dose in gastric intubation studies and inversely correlated with the dose in dietary studies. The carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (CAS: 24554-26-5) was fed to male and female CD-1 mice in the diet as a positive control. The predominant tumor observed in these groups was transitional cell carcinoma of the bladder. These data indicate that SQ18506 is unsuitable for use in the treatment of parasitic diseases.
Subject(s)
5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/toxicity , Carcinogens , Neoplasms, Experimental/pathology , Nitrofurans/toxicity , Schistosomiasis/drug therapy , 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/therapeutic use , Aging , Animals , Dose-Response Relationship, Drug , Female , Male , Mice , Neoplasms, Experimental/chemically induced , Schistosoma mansoniABSTRACT
The activity of the 5-nitrovinylfuran, SQ 18 506, is compared in vivo and in vitro with lampit (a 5-nitrofuran), Ro 7-1051 (a 2-nitroimidazole) and metronidazole (a 5-nitroimidazole). The order of activities on a weight basis was: SQ 18 506 greater than lampit greater than Ro 7-1051 greater than metronidazole. Concern about possible mutagenicity and carcinogenicity, however, has precluded the use of SQ 18 506 in clinical trials.
Subject(s)
5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/therapeutic use , Chagas Disease/drug therapy , Nitrofurans/therapeutic use , 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/adverse effects , Animals , Culture Techniques , Drug Evaluation, Preclinical , Female , Male , Metronidazole/therapeutic use , Mice , Mice, Inbred A , Nitroimidazoles/therapeutic useABSTRACT
Nine of 25 carefully selected compounds (from a stock of more than 200 000 chemical species amassed principally as a result of testing against other parasitic diseases) were found to have significant suppressive activity against the parasites in the blood of a Trypanosoma cruzi mouse model. Eight of these compounds evaluated in this model had suppressive activity equal to or greater than the reference compound, nifurtimox. For the first time, suppressive activity against T. cruzi is reported for a 7-aminoquinoline, a phosphonium salt, and TAC pamoate; The biological model is believed to be able to serve as a means of identifying other new "leads* in seeking drugs broadly effective against T=ruzi infections in man.
Subject(s)
Chagas Disease/drug therapy , Disease Models, Animal , Trypanocidal Agents/therapeutic use , 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/pharmacology , 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/therapeutic use , Aminoquinolines/pharmacology , Aminoquinolines/therapeutic use , Animals , Chagas Disease/parasitology , Male , Mice , Nifurtimox/therapeutic use , Onium Compounds/pharmacology , Onium Compounds/therapeutic use , Structure-Activity Relationship , Trityl Compounds/pharmacology , Trityl Compounds/therapeutic use , Trypanosoma cruzi/drug effectsSubject(s)
Schistosomiasis/drug therapy , Schistosomicides/therapeutic use , 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole/therapeutic use , Adult , Animals , Antimony/therapeutic use , Child , Cricetinae , Humans , Hycanthone/adverse effects , Hycanthone/therapeutic use , Mice , Niridazole/adverse effects , Niridazole/therapeutic use , Rats , Tubercidin/therapeutic useABSTRACT
A new antimicrobial nitrofuran designated SQ 18,506 showed some therapeutic activity when administered orally to mice infected with Escherichia coli, Salmonella schottmuelleri, Shigella flexneri, or Klebsiella pneumoniae. Animals infected parenterally with Streptococcus pyogenes, Proteus mirabilis, Mycobacterium tuberculosis, and Candida albicans, or topically with Trichophyton mentagrophytes, did not respond to therapy with the drug at the dosage levels used. The compound was as effective as metronidazole in the topical treatment of experimental trichomonal infections in mice and in guinea pigs and as effective as nystatin, candicidin, or a sulfanilamide-aminacrine hydrochloride cream in the treatment of a candidal vaginal infection in rats. The chemotherapeutic efficacy of SQ 18,506 in experimental vaginitis caused by Escherichia coli in the rat surpassed that shown by four commercial products available for the treatment of bacterial vaginitis.