Antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds.
A small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. All tested compounds were active or moderately active against Trypanosoma cruzi amastigotes in infected L6 cells and Trypanosoma brucei brucei, four of eleven compounds were moderately active against Leishmania donovani axenic parasites while none were deemed active against T. brucei rhodesiense. For the most active/moderately active compounds a moderate selectivity against each parasite was observed. There was good correlation between lipophilicity (clogP value) and antileishmanial activity or toxicity against L6 cells. Similarly, good correlation existed between clogP values and IC50 values against T. cruzi in structurally related subgroups of compounds. Three compounds were more potent as antichagasic agents than benznidazole but were not activated by the type I nitrorectusase (NTR).
NorthShore University HealthSystem, Evanston, IL, USA. Electronic address: mvpapadopoulou@gmail.com.
Maria V
MV
Papadopoulou
NorthShore University HealthSystem, Evanston, IL, USA.
William D
WD
Bloomer
Oakton Community College, Des Plaines, IL, USA.
Howard S
HS
Rosenzweig
School of Biological & Chemical Sciences, Queen Mary University of London, London, UK.
Shane R
SR
Wilkinson
School of Biological & Chemical Sciences, Queen Mary University of London, London, UK.
Joanna
J
Szular
Swiss Tropical and Public Health Institute, Parasite Chemotherapy, Basel, Switzerland; University of Basel, Basel, Switzerland.
Marcel
M
Kaiser
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy*; D006801:Humans; D007891:Leishmania / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014345:Trypanosoma / Q000187:drug effects
D000577:Amides; D000981:Antiprotozoal Agents; D013844:Thiazoles; D014344:Trypanocidal Agents; C004483:2-aminothiazole
5-Nitro-2-aminothiazoles; Antitrypanosomal agents; Chagas disease; Leishmania; MZSRZQZBRGCXDO-UHFFFAOYSA-N; Type I nitroreductase