Synthesis and antichagasic properties of new 1,2,6-thiadiazin-3,5-dione 1,1-dioxides and related compounds.
In a search for antichagasic drugs, 14 new 4-(nitroarylidene)-1,2,6-thiadiazin-3,5-dione 1,1-dioxide derivatives were synthesized and tested in vitro against the epimastigote form of Trypanosoma cruzi and some of them showed important antiprotozoan activity. Attempts to synthesize new 4-(nitroarylidene)-3,5-diamino-1,2,6-thiadiazine 1,1-dioxides were unsuccessful. The antichagasic properties of nitroarylidene-malononitrile and nitroarylidene-cyanoacetamide derivatives, thus obtained, were also tested. The cytotoxic properties against Vero cells of compounds which showed remarkable in vitro antichagasic activity were evaluated. All compounds tested exhibited high toxicity percentages at 100 micrograms/ml. However, compound 3c showed in vitro antichagasic and cytotoxic properties such as nifurtimox at the dose of 10 micrograms/ml.
Di Maio
R
R
Cátedra de Química Orgánica, Facultad de Química y Ciencias, Universidad de la República, Montevideo, Uruguay.
Cerecetto
H
H
Seoane
G
G
Ochoa
C
C
Arán
V J
VJ
Pérez
E
E
Gómez Barrio
A
A
Muelas
S
S
D000818:Animals; D002522:Chlorocebus aethiops; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009547:Nifurtimox / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013829:Thiadiazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects; D014709:Vero Cells
C400196:2,6-dihexyl-(2,3,5,6-tetrahydro)-1,2,6-thiadiazin-3,5-dion 1,1-dioxide; D009593:Nitroimidazoles; D013829:Thiadiazines; D014344:Trypanocidal Agents; D009547:Nifurtimox; C009999:benzonidazole