Synthesis, antimycobacterial, cytotoxicity, anti-inflammatory, in silico studies and molecular dynamics of pyrazole-embedded thiazolidin-4-one hybrids

Arch Pharm (Weinheim). 2023 Mar;356(3):e2200444. doi: 10.1002/ardp.202200444. Epub 2022 Dec 2.

Abstract

In the present investigation, we devolved and synthesized a new series of pyrazole-embedded thiazolidin-4-one derivatives (9a-p) with the goal to produce promising antitubercular leads. The in vitro antimycobacterial activity of the synthesized compounds was tested against replicating and nonreplicating Mtb H37Rv strains. With MIC ranging from 3.03 to 22.55 µg/ml, five compounds (9a, 9c, 9d, 9e, and 9f) emerged as promising antitubercular agents. The active molecules were nontoxic to normal Vero cells. All the synthesized compounds were evaluated for in vitro anti-inflammatory studies. Compounds 9a, 9b, 9c, 9h, and 9i exhibited excellent anti-inflammatory efficacy. Docking study was performed to understand the binding pattern of the significantly active compound 9a with 1P44.

Keywords: Alamar blue solution; anti-inflammatory; antimycobacterial; thiazolidin-4-one.

MeSH terms

  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Chlorocebus aethiops
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation*
  • Molecular Structure
  • Mycobacterium tuberculosis*
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Antitubercular Agents
  • Pyrazoles