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 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.
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2-(Cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5H)-one

Multicomponent reactions effectively contribute to modern organic and medicinal chemistry. 4-Thiazolidinone core and cyclopropyl moiety are important structural motifs for design of potential biologically active molecules. In the present paper, the convenient step-economy and cost-effective synthesis of 2-(cyclopropylamino)-5-(4-methoxybenzylidene)thiazol-4(5H)-one (2) is described based on the application of the MCR methodology. The proposed approach includes direct one-pot interaction of 2-thioxothiazolidin-4-one (rhodanine), 4-methoxybenzaldehyde with cyclopropylamine which was used in 10% excess compare to other reagents. The structure of synthesized compound 2 was confirmed using 1H, 13C, 2D NMR, LC-MS, IR and UV spectra. The presence of prototropic amino/imino tautomerism for synthesized compound 2 was observed based on spectral analysis data. Screening of antimicrobial activity against 12 strains of Gram-positive and Gram-negative bacteria, as well as yeasts, was performed for synthesized derivative 2. © 2022 by the authors.

Author keywords

4-thiazolidinones; antimicrobial activity; cyclopropylamine; multicomponent reactions; rhodanine
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1,4-Naphthoquinone Motif in the Synthesis of New Thiopyrano[2,3-d]thiazoles as Potential Biologically Active Compounds

A series of 11-substituted 3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones were obtained via hetero-Diels-Alder reaction of 5-alkyl/arylallylidene/-4-thioxo-2-thiazolidinones and 1,4-naphthoquinones. The structures of newly synthesized compounds were established by spectral data and a single-crystal X-ray diffraction analysis. According to U.S. NCI protocols, compounds 3.5 and 3.6 were screened for their anticancer activity; 11-Phenethyl-3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d]thiazole-2,5,10-trione (3.6) showed pronounced cytotoxic effect on leukemia (Jurkat, THP-1), epidermoid (KB3-1, KBC-1), and colon (HCT116wt, HCT116 p53-/-) cell lines. The cytotoxic action of 3.6 on p53-deficient colon carcinoma cells was two times weaker than on HCT116wt, and it may be an interesting feature of the mechanism action.
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