Biopolym. Cell. 2020; 36(2):133-145.
http://dx.doi.org/10.7124/bc.000A27
Bioorganic Chemistry
Synthesis and evaluation of biological activity of rhodanine-pyrazoline hybrid molecules with 2-(2,6-dichlorophenylamino)-phenylacetamide fragment
1Shepeta Yu. L., 2Lozynskyi A. V., 2Tomkiv Z. V., 3Grellier P., 2, 4Lesyk R. B.
  1. National Pirogov Memorial Medical University NAMS of Ukraine
    56, Pirogova Str., Vinnytsya, Ukraine, 21018
  2. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  3. National Museum of Natural History, UMR 7245 CNRS MCAM, Sorbonne Universités
    CP 52, 57 Rue Cuvier, Paris 75005, France
  4. University of Information Technology and Management in Rzeszow
    2, Sucharskiego Str., Rzeszow, Poland, 35-225

Abstract

Aim. Synthesis of new rhodanine-pyrazoline hybrid molecules with a diclofenac fragment in position 3 using the reactions of heterocyclization and aminolysis with potential antitumor and antitrypanosomal activities. Methods. Organic synthesis, NMR spectroscopy, pharmacological screening. Results. The reaction between 2-(2,6-dichloro-phenyl-amino)-phenylacetic acid hydrazide and thiocarbonyl-bis-thioglycolic acid in ethanol medium providing rhodanine derivative with fragment of the anti-inflammatory drug diclofenac in position 3 was performed. The presence of an active methylene group in position 5 and its subsequent modification providing 5-ethoxymethylenerhodanine and further aminolysis reaction with various 3,5-diaryl-4,5-dihydro-1H-pyrazoles allowed to produce of a series of 5-(3,5-diaryl-4,5-dihydropyrazol-1-ylmethylene)-2-thioxothiazolidin-4-ones. The antitumor activity screening allowed to identify highly active compound 9 with a mean GI50 = 0.71/1.09 and TGI = 82.95/28.46 μM towards 60 cancer lines (DTP NCI program). The synthesizedpyrazoline-thiazolidinehybrid molecules with the diclofenac fragment in the structure did not show significant antitrypanosomal activity against Trypanosoma brucei brucei (Tbb). Conclusions. The synthesized 5-(3,5-diaryl-4,5-dihydropyrazol-1-ylmethylene)-2-thioxothiazolidin-4-ones with a diclofenac fragment in the structure are a promising molecular platform for creation of new highly active potential drugs with a low-toxicity.
Keywords: synthesis, 2-thioxo-4-thiazolidinone, diclofenac, spectral data, antitumor activity, an-titrypanosomal activity
Full text: (PDF, in English)

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