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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number130863
Number of pages11
JournalJournal of Molecular Structure
Volume1243
DOIs
StatePublished - 5 Nov 2021

Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Inorganic Chemistry

Keywords

  • 2H-Pyrazol-3-ols
  • Anti-tubercular activity
  • Aromatic aldehydes
  • Knoevenagel condensation
  • Molecular docking
  • Structure

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