Biopolym. Cell. 2019; 35(6):437-447.
Bioorganic Chemistry
Synthesis and in vivo evaluation of pyrazoline-thiazolidin-4-one hybrid Les-5581 as a potential non-steroidal anti-inflammatory agent
1, 2, 3Holota S. M., 4Derkach H. O., 1Demchuk I. L., 4Vynnytska R. B., 1Antoniv O. I., 5Furdychko L. O., 2Slyvka N. Yu., 1Nektegayev I. O., 1, 6Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Lesya Ukrainka Eastern European National University
    13, Volya Av, Lutsk, Ukraine, 43025
  3. Lviv Medical Institute
    76, V. Polischuk Str., Lviv, Ukraine, 79018
  4. Ivano-Frankivsk National Medical Universitу
    2, Halytska Str., Ivano-Frankivsk, Ukraine, 76018
  5. Bogomolets National Medical University
    13, Shevchenko Blvd., Kyiv, Ukraine, 01601
  6. University of Information Technology and Management in Rzeszow
    2, Sucharskiego Str., Rzeszow, Poland, 35-225

Abstract

Aim. Synthesis and study in vivo of acute toxicity, anti-inflammatory (anti-exudative) activity and evaluation of side effects of pyrazoline-thiazolidin-4-one hybrid Les-5581 under conditions of therapeutic use in experimental animals. Methods. Traditional organic synthesis. The Litchfield - Wilcoxon method. Carrageenin- and formaldehyde-induced inflammatory paw edema models of white rats. Clinical laboratory tests: study of general blood parameters and biochemical profile of liver function (ALT, AST, LF and γ-GGT levels). Evaluation of ulcerogenic action. Results. The target hybrid Les-5581 has been synthesized in convenient and efficient aminolysis of 5-etoxymethylidenerhodanine by 3,5-bis-(4-chloro-phenyl)-4,5-dihydro-1H-pyrazole. The LD50 value for Les-5581 was determined with intraperitoneal use and it was 510 mg/kg. The Les-5581 exhibits significant anti-inflammatory activity at a dose of 50 mg/kg (intraperitoneal use) in [the] experiment on carrageenin- and formaldehyde-induced inflammatory models in white rats. At the same time, the use of Les-5581 does not provoke a negative impact on the blood pattern, the liver enzymes function and has no ulcerogenic effect. Conclusions. The pyrazoline-thiazolidine-4-one hybrid Les-5581 is a good molecular platform for the development of new potential low-toxicity anti-inflammatory drugs without ulcerogenic action.
Keywords: pyrazoline, thiazolidin-4-one, NSAIDs, molecular hybrid

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