The aim of work: to synthesize 5-alkyl-substituted 2-hydrazono-4-thiazolidinones with a 6-arylimidazo[2,1-b][1,3,4]thiadiazole fragment in the molecules and to study the antitrypanosomal activity of the synthesized compounds.

Materials and methods. Organic synthesis, NMR spectroscopy, elemental analysis, and pharmacological screening were performed.

Results. A convenient and effective method for the formation of a 4-thiazolidinone ring is the [2+3]-cyclocondensation reaction of S,N-binucleophiles with different equivalents of the dielectrophilic synthon [C2]2+. Following the above concept, we obtained a series of targeted 5-alkyl-substituted 2-methylidenehydrazino-4-thiazolidinones with a 6-arylimidazo[2,1-b][1,3,4]thiadiazole fragment in molecules 6a–e and 7a–b by the interaction of N1-(6-arylimidazo[2,1-b][1,3,4]thiadiazol-5-ylmethylidene)-thiosemicarbazones 5a–c with α-halocarboxylic (monochloroacetic, 2-bromopropionic, 2-bromobutanoic) acids or α-bromo-γ-butyrolactone in acetic acid and the presence of sodium acetate. The structure of the synthesized compounds was confirmed by elemental analysis and NMR spectroscopy.

Conclusions. The results of in vitro screening of antitrypanosomal activity against Trypanosoma brucei gambiense (TBG) allowed us to identify two highly active compounds 6c and 7b, which exhibited essential trypanocidal effect with IC50 values of 3.7 µM and 3.2 µM, respectively.