NEW NON-CONDENSED PYRIDINE-THIAZOLE/THIAZOLIDINONES AND THEIR ANTITRYPANOSOMAL ACTIVITY
DOI:
https://doi.org/10.11603/2312-0967.2017.2.7911Keywords:
synthesis, 4-thiazolidinone, [2 3]-cyclocondensation, spectral characteristics, antitrypanosomal activity.Abstract
The aim of the work. Synthesis of new non-condenced pyridine-thiazole/thiazolidinones and study of their antitrypanosomal activity in vitro.
Materials and Methods. All starting materials were purchased from commercial sourses and used without purification. The 1H and 13C NMR spectra were recorded on a Varian Gemini 400-MHz and Varian Mercury-400 100 MHz instruments. LC-MS spectra were obtained on a Agilent 1100 Series LCMS. Melting points are uncorrected and were measured in open capillary tubes on a BUCHI B-545 melting point apparatus.
Results and Discussion. Series of thiazole, thiazoline and 5-substituted 4-thiazolidinones containing pyridine fragment were synthesized using reactions of [2+3]-cyclocondensations. Thiosemicarbazones of 3- and 4-peridinecarbaldehyses as S,N-binucleophiles and some equivalents of dielectrophilic synthone [C2]2+ (α-halogen-carboxylic acids, ethyl-2-chloroacetoacetate, methyl-2-bromo-3-(3methylphenyl)propionate and maleimides) were used. Antitrypanosomal activity screening in vitro on the Trypanosoma brucei gambiense strain allowed to identify highly active non-condensed furan-pyridine-thiazoline derivative with trypanocide effect in micromolar concentrations (IC50 = 3.32 mM), and 5-ethyl-2-(pirydynilmethylenhidrazyne)thiazol-4-ones with promising activity for further optimization.
Conclusions. New non-condensed pyridine-thiazole/thiazolidinones as promising drugs for pharmacotherapy of sleeping sickness were obtained.References
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