Synthesis and Antichagasic Properties of New 1,2,6-Thiadiazin-3,5-dione 1,1-Dioxides and Related Compounds

• Published in: Arzneimittel-Forschung Vol. 49; no. 9; pp. 759 - 763
• Main Authors: Maio, Rossanna Di, Cerecetto, Hugo, Seoane, Gustavo, Ochoa, Carmen, Arán, Vicente J, Pérez, Eduardo, Barrio, Alicia Gómez, Muelas, Susana
• Format: Journal Article
• Language: English
• Published: Aulendorf (Germany) Editio Cantor Verlag 01-09-1999; Cantor
• Subjects: Animals; Antibacterials; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Cercopithecus aethiops; Chemotherapeutics; Cytostatics; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Nifurtimox - chemistry; Nifurtimox - pharmacology; Nifurtimox - toxicity; Nitroimidazoles - chemistry; Nitroimidazoles - pharmacology; Nitroimidazoles - toxicity; Pharmacology. Drug treatments; Spectrophotometry, Infrared; Thiadiazines - chemical synthesis; Thiadiazines - pharmacology; Thiadiazines - toxicity; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanocidal Agents - toxicity; Trypanosoma cruzi - drug effects; Vero Cells; 4-Nitroarylidene-1,2,6-thiadiazin-3,5-dione 1,1-dioxides, in vitro studies, synthesis; Nitroarylidene-malononitriles, in vitro studies, synthesis; Antichagasic drugs; Nitroarylidene-cyanoacetamides, in vitro studies, synthesis; Kinetoplastida; Protozoa; Drug susceptibility test; Cytotoxicity; In vitro; Biological activity; Research and development; Trypanosoma cruzi; Antiprotozoal agent; Epimastigote; Parasiticid; Established cell line; Hemisynthesis
• ISSN: 0004-4172; 1616-7066
• DOI: 10.1055/s-0031-1300498

Summary
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 µg/ml. However, compound
3c
showed in vitro antichagasic and cytotoxic properties such as nifurtimox at the dose of 10 µg/ml.