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

• Main Authors: Andrii Lozynskyi (Author), Yulian Konechnyi (Author), Julia Senkiv (Author), Ihor Yushyn (Author), Dmytro Khyluk (Author), Olexandr Karpenko (Author), Yulia Shepeta (Author), Roman Lesyk (Author)
• Format: Book
• Published: MDPI AG, 2021-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/scipharm89040052; 2218-0532; 0036-8709
• Keywords: thiazolo[4,5-<i>b</i>]pyridines; antimicrobial activity; pharmacokinetics prediction; molecular docking; Pharmacy and materia medica; RS1-441
• Source: Scientia Pharmaceutica, Vol 89, Iss 4, p 52 (2021)

A series of 5-methyl-7-phenyl-3<i>H</i>-thiazolo[4,5-<i>b</i>]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 <b>3g</b>, which displayed the potent inhibitory effect against <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i> with MIC value of 0.21 μM. The active thiazolopyridine derivatives <b>3c</b>, <b>3f</b>, and <b>3g</b> were screened for their cytotoxicity effects on HaCat, Balb/c 3T3 cells using MTT assay, which revealed promising results. In silico assessment for compounds <b>3c</b>, <b>3f</b>, and <b>3g</b> also revealed suitable drug-like parameters and ADME properties. The binding interactions of the most active compound <b>3g</b> 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-<i>b</i>]pyridines constitute an exciting background for the further development of new synthetic antimicrobial agents.