Синтез і дослідження антитрипаносомної активності 5-алкіл-2-метиліденгідразоно-4-тіазолідинонів з 6-арилімідазо[2,1-b]тіадіазольним фрагментом у молекулах

M. I. Lelyukh; I. H. Chaban; A. A. Savchenko; O. Y. Komarytsya; T. I. Chaban

doi:10.14739/2409-2932.2025.3.339291

Authors

M. I. Lelyukh Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0000-0002-8123-0988
I. H. Chaban Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0000-0002-5146-5655
A. A. Savchenko Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0000-0001-5809-8686
O. Y. Komarytsya Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0009-0002-9185-1304
T. I. Chaban Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0000-0003-0618-275X

DOI:

https://doi.org/10.14739/2409-2932.2025.3.339291

Keywords:

2-hydrazono-4-thiazolidinones, 6-arylimidazo[2,1-b][1,3,4]thiadiazoles, heterocyclization reaction, spectral data, antitrypanosomal activity

Abstract

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.

Author Biographies

M. I. Lelyukh, Danylo Halytsky Lviv National Medical University

PhD, Senior Lecturer of the Department of Pharmaceutical, Organic and Bioorganic Chemistry

I. H. Chaban, Danylo Halytsky Lviv National Medical University

PhD, Associate Professor of the Department of Pharmaceutical, Organic and Bioorganic Chemistry

A. A. Savchenko, Danylo Halytsky Lviv National Medical University

MD, PhD, Associate Professor of the Department of Surgery No. 2

O. Y. Komarytsya, Danylo Halytsky Lviv National Medical University

MD, PhD, Associate Professor of the Department of Surgical and Orthopedic Dentistry, Faculty of Postgraduate Education

T. I. Chaban, Danylo Halytsky Lviv National Medical University

PhD, Associate Professor of the Department of General, Bioinorganic, Physical and Colloidal Chemistry

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