5-[4-(tert-Butyl)cyclohexylidene]-2-thioxothiazolidin-4-one

The Knoevenagel reaction is an essential synthetic tool in the organic and medicinal chemistry of thiazolidin-4-one derivatives. In the present work, the application of ethylenediamine diacetate (EDDA) as an effective catalyst for the interaction of 2-thioxothiazolidin-4-one with 4-(tert-butyl)cyclohexanone is proposed. The structure of novel synthesized 5-[4-(tert-butyl)cyclohexylidene]-2-thioxothiazolidin-4-one (yield 61%) was confirmed by 1H-, 13C-NMR, LC-MS, IR, and UV spectra. Drug-like properties of the synthesized compound were evaluated in silico using the SwissAdme, and their potential antimicrobial activity against 15 strains of Gram-positive and Gram-negative bacteria as well as yeasts was evaluated in vitro. The synthesized compound possesses satisfactory drug-like parameters and promising antimicrobial properties and presents interest as a prospective intermediate for the forthcoming design of biologically active small molecules

5-[4-(<i>tert</i>-Butyl)cyclohexylidene]-2-thioxothiazolidin-4-one

The Knoevenagel reaction is an essential synthetic tool in the organic and medicinal chemistry of thiazolidin-4-one derivatives. In the present work, the application of ethylenediamine diacetate (EDDA) as an effective catalyst for the interaction of 2-thioxothiazolidin-4-one with 4-(tert-butyl)cyclohexanone is proposed. The structure of novel synthesized 5-[4-(tert-butyl)cyclohexylidene]-2-thioxothiazolidin-4-one (yield 61%) was confirmed by 1H-, 13C-NMR, LC-MS, IR, and UV spectra. Drug-like properties of the synthesized compound were evaluated in silico using the SwissAdme, and their potential antimicrobial activity against 15 strains of Gram-positive and Gram-negative bacteria as well as yeasts was evaluated in vitro. The synthesized compound possesses satisfactory drug-like parameters and promising antimicrobial properties and presents interest as a prospective intermediate for the forthcoming design of biologically active small molecules

Analysis of carbohydrates content in the plant components of antidiabetic herbal mixture by GC-MS

Medicinal plants and their combinations due to the wide range of biologically active substances can influence on various links of the pathogenetic mechanism of development of diabetes mellitus and its complications. One of such combinations is an antidiabetic herbal mixture (Urticae folia, Rosae frucrus, Myrtilli folia, Menthae folia and Taraxaci radices) with established hypoglycemic, hypolipidemic, antioxidant, hepatoprotective, pancreatoprotective activity in previous pharmacological study in vivo. Thus, the aim of this study was to identify and establish the content of carbohydrates in free and bound form in the plant components of antidiabetic herbal mixture. The carbohydrates were separated by gas chromatography-mass spectrometry after conversion into volatile derivatives as aldononitrile acetate. The monomeric composition of polysaccharides was studied after their hydrolysis to form monosaccharides and polyalcohols. The results of the quantitative study showed that the predominant carbohydrate in free form was saccharose in Urticae folia, L-fructose in Myrtilli folia, Rosae frucrus, Taraxaci radices and Menthae folia, L-glucose in Rosae frucrus. Concerning the determination of monomers of polysaccharides after hydrolysis, L-glucose prevailed in all plant components of antidiabetic herbal mixture. The chromatographic study revealed a number of polyalcohols that are important for the treatment and prevention of progression of diabetes mellitus and its complications, namely, mannitol and myo-inositol

Synthesis and Biological Activity Evaluation of Novel 5-Methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones

A series of 5-methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones has been designed, synthesized, and characterized by spectral data. Target compounds were screened for their antimicrobial activity against some pathogenic bacteria and fungi, and most of them showed moderate activity, especially compound 3g, which displayed the potent inhibitory effect against Pseudomonas aeruginosa and Escherichia coli with MIC value of 0.21 &mu;M. The active thiazolopyridine derivatives 3c, 3f, and 3g were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds 3c, 3f, and 3g also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound 3g were performed through molecular docking against MurD and DNA gyrase, with binding energies and an inhibitory constant compared to the reference drug ciprofloxacin. The tested thiazolo[4,5-b]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents

Synthesis and Biological Activity Evaluation of Novel 5-Methyl-7-phenyl-3<i>H</i>-thiazolo[4,5-<i>b</i>]pyridin-2-ones

A series of 5-methyl-7-phenyl-3H-thiazolo[4,5-b]pyridin-2-ones has been designed, synthesized, and characterized by spectral data. Target compounds were screened for their antimicrobial activity against some pathogenic bacteria and fungi, and most of them showed moderate activity, especially compound 3g, which displayed the potent inhibitory effect against Pseudomonas aeruginosa and Escherichia coli with MIC value of 0.21 μM. The active thiazolopyridine derivatives 3c, 3f, and 3g were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds 3c, 3f, and 3g also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound 3g were performed through molecular docking against MurD and DNA gyrase, with binding energies and an inhibitory constant compared to the reference drug ciprofloxacin. The tested thiazolo[4,5-b]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents

Multi-Targeting Anticancer Activity of a New 4-Thiazolidinone Derivative with Anti-HER2 Antibodies in Human AGS Gastric Cancer Cells

Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1—were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells