2-(2-Amino-6-methylpyrimidin-4-yl)-4-arylmethylidene- 5-methyl-2,4-dihydro-3H-pyrazol-3-ones: Design, synthesis, structure, in vitro anti-tubercular activity, and molecular docking study

Andrei V. Erkin, Aleksandra V. Yurieva, Oleg S. Yuzikhin, Vladislav V. Gurzhiy, Viktor I. Krutikov

Результат исследований: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

A series of 2-(2-amino-6-methylpyrimidin-4-yl)-4-arylmethylidene-2,4-dihydro-3H-pyrazol-3-ones 6a-f was in silico predicted to display moderate anti-tubercular activity. To obtain these compounds, the Knoevenagel condensation of the corresponding pyrazol-3-ol 10 with aromatic aldehydes was performed. It was found that arylidenepyrazolones 6b, 6d and 6e bearing 4-diethylamino (6b), 3,4-dimethoxy (6d) and 4-hydroxy-3-methoxy (6e) substituents on the arylidene pendant did possess activity against Mycobacterium tuberculosis H37Rv. Their minimal inhibitory concentrations (MICs = 0.07-0.14 mmol/L) were comparable with MIC value for isoniazid (0.01 mmol/L) used as the reference drug. In accordance with a molecular docking study, a plausible mode of action of arylidenepyrazolones 6b, 6d and 6e was the inhibition of UDP-galactopyranose mutase responsible for the biosynthesis of arabinogalactan, one of the important components of the mycobacterial cell wall. The above results indicated that compounds 6b, 6d and 6e might serve as promising hits in further search for anti-tubercular agents based thereon.

Язык оригиналаанглийский
Номер статьи130863
ЖурналJournal of Molecular Structure
Том1243
DOI
СостояниеОпубликовано - 5 ноя 2021

Предметные области Scopus

  • Аналитическая химия
  • Спектроскопия
  • Органическая химия
  • Неорганическая химия

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