Synthesis and in vivo evaluation of pyrazoline-thiazolidin-4-one hybrid Les-5581 as a potential non-steroidal anti-inflammatory agent

Abstract

Aim. Synthesis and in vivo study of acute toxicity, anti-inflammatory (anti-exudative) activity and 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 a 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. Les-5581 exhibits significant anti-inflammatory activity at a dose of 50 mg/kg (intraperitoneal use) in an experiment on carrageenin-and formaldehyde-induced inflammatory models in white rats. 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 development of new potential lowtoxicity anti-inflammatory drugs without ulcerogenic action. K e y w o r d s: pyrazoline, thiazolidin-4-one, NSAIDs, molecular hybrid

Systematic Review on Thiazole Compounds as Nanoparticles: Chemistry, Synthesis, Antimicrobial Activities, Therapeutic Investigation

“…(5) was reported as Alzheimer's diseases-related glycogen synthase kinase inhibitor, which prevented neurological mitochondrial apoptosis and reduced inflammation [100,101]. (5).…”

Synthesis, Characterization and In Vitro Evaluation of Novel 5-Ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones as Possible Anticancer Agents

“…Thereby, by the three-component reaction of 1 with chloroacetic acid and aromatic/heteroaromatic aldehydes in a mixture AcONa + AcOH:Ac2O employing convenient heating resulted in compounds 2a-l (Scheme 1) which were purified by recrystallization. In view of our interest in the search for and study of new low-molecular heterocyclic modulators among thiazole-bearing molecules [31][32][33][34], herein, we report the synthesis, structure characterization and in vitro anticancer activity evaluation of some novel heterocyclic derivatives. This manuscript is intended to draw attention towards the chemistry and pharmacology of the 5-ene-thiazolo [3,2-b][1,2,4]triazole-6(5H)-one fragment and its further exploration as a prospective source of drug-like molecules.…”

Synthesis of novel pyrazoline-thiazolidin-4-one hybrids and evaluation their biological activity

“…In our early-described researches some types thiazolidin-4-one hybrids linked through "enamine" linker at C-5 has been synthesized and several compounds been have been identified with a high level of antibacterial and antifungal [12][13][14], anticancer and trypanocidal [15], and antiinflammatory activity [16] (Figure 1). In our opinion, the 5-aminomethylidene derivatives have several important advantages in synthetic variability and structure optimization processes compared to 5-ylidene analogous.…”