Synthesis, and biological evaluation of new 1,3,4-thiadiazolium-2-phenylamine derivatives against Leishmania amazonensis promastigotes and amastigotes

• Published in: European journal of medicinal chemistry Vol. 37; no. 12; pp. 979 - 984
• Main Authors: da Silva, Edson F, Canto-Cavalheiro, Marilene M, Braz, Viviane R, Cysne-Finkelstein, Léa, Leon, Leonor L, Echevarria, Aurea
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Masson SAS 01-12-2002; Elsevier
• Subjects: 1,3,4-thiadiazolium-2-aminide; Aniline Compounds - chemical synthesis; Aniline Compounds - chemistry; Aniline Compounds - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; antileishmanial activity; Antiparasitic agents; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Design; Leishmania braziliensis - drug effects; Leishmania braziliensis - growth & development; Magnetic Resonance Spectroscopy; Medical sciences; mesoionic compounds; Models, Molecular; Molecular Conformation; Pharmacology. Drug treatments; Structure-Activity Relationship; antileishmanial activity; mesoionic compounds; 1,3,4-thiadiazolium-2-aminide; Kinetoplastida; Protozoa; Sulfur nitrogen heterocycle; Five membered ring; Organic cation; Benzene derivatives; In vitro; Antiprotozoal agent; Structure activity relation; Leishmania; Parasiticid; Chemical synthesis; Amastigote; Promastigote
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(02)01401-0

1,3,4-Thiadiazolium-2-aminide, which is a class of mesoionic compounds, were tested against promastigote and amastigote forms of
Leishmania amazonensis. Parasites were assayed with or without the drugs in axenic media, using pentamidine isethionate as a reference drug. The very promising results showed us the most active compounds were the 4′- and 3′-methoxy derivatives against promastigote forms, while the highest activity against the amastigote forms was obtained with the 4′-fluor and 3′-bromo derivatives.