SYNTHESIS AND ANTITRYPANOSOMAL ACTIVITY INVESTIGATION OF NOVEL 5-YLIDENE-2-(1,3,4-THIADIAZOL-2-YL)IMINOTHIAZOLIDIN-4-ONES

Authors

  • M. I. Lelyukh Danylo Halytsky Lviv National Medical University
  • B. S. Zimenkovsky Danylo Halytsky Lviv National Medical University
  • I. L. Demchuk Danylo Halytsky Lviv National Medical University
  • Philippe Grellier National Museum of Natural History
  • R. B. Lesyk Danylo Halytsky Lviv National Medical University

DOI:

https://doi.org/10.11603/2312-0967.2017.3.8037

Keywords:

2-iminothiazolidin-4-ones, 1, 3, 4-thiadiazoles, heterocyclization reaction, amino-imino tautomerism, Knoevenagel condensation, E/Z-isomerism, spectral data, antitrypanosomal activity.

Abstract

The aim of work. Synthesize the new thiadiazolo-2-iminothiazolidin-4-ones and their 5-arylidene derivatives based on the heterocyclization reaction and Knoevenagel condensation and study their antitrypanosomal activity.

Materials and Methods: organic synthesis, NMR spectroscopy, elemental analysis, pharmacological screening.

Results and Discussion. Following the cyclization reaction of N-(1,3,4-thiadiazol-2-yl)substituted 2-chloroacetamides with ammonium thiocyanate in dry acetone the corresponding 2-imino-4-thiazolidinone derivatives have been obtained. Further chemical modification of synthesized methylene active 2-(1,3,4-thiadiazol-2-yl)imino-4-thiazolidinones was performed via Knoevenagel condensation with various aromatic or heterocyclic aldehydes, isatin or cinnamic aldehyde derivatives have yielded a series of 5-aryl(heteryl)ylidene- and 5-isatin(3-phenylpropene)ylidene derivatives as potential antitrypanosomal agents. The structure of obtained compounds was confirmed by NMR spectroscopy and elemental analysis.

Conclusions. The results of in vitro screening of antitrypanosomal activity against Trypanosoma brucei gambiense (TBG) allowed us to identify four highly active compounds which owned essential trypanocidal effect with a range of values IC50 within 7.3-12.8 µM.

Author Biographies

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

Teaching Assistant, Department of Pharmaceutical Chemistry, Faculty of Postgraduate Education, Danylo Halytsky Lviv National Medical University, PhD

B. S. Zimenkovsky, Danylo Halytsky Lviv National Medical University

Chancellor of Danylo Halytsky Lviv National Medical University, PhD, DSc, Professor of the Department of Pharmaceutical, Organic and Bioorganic Chemistry

I. L. Demchuk, Danylo Halytsky Lviv National Medical University

Associate Professor, Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, PhD

Philippe Grellier, National Museum of Natural History

Head of the Scientific Group UMR 7245 CNRS Molécules de Communication et Adaptation des Microorganismes», National Museum of Natural History

R. B. Lesyk, Danylo Halytsky Lviv National Medical University

Head of the Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, PhD, DSc, Professor

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Published

2017-10-04

How to Cite

Lelyukh, M. I., Zimenkovsky, B. S., Demchuk, I. L., Grellier, P., & Lesyk, R. B. (2017). SYNTHESIS AND ANTITRYPANOSOMAL ACTIVITY INVESTIGATION OF NOVEL 5-YLIDENE-2-(1,3,4-THIADIAZOL-2-YL)IMINOTHIAZOLIDIN-4-ONES. Pharmaceutical Review Farmacevtičnij časopis, (3), 5–12. https://doi.org/10.11603/2312-0967.2017.3.8037

Issue

No. 3 (2017)

Section

Synthesis of biologically active compounds

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