Pyrazoline analogues: Design, synthesis, and evaluation of anti-osteoporosis activity

Bioorg Med Chem Lett. 2022 Mar 15:60:128585. doi: 10.1016/j.bmcl.2022.128585. Epub 2022 Jan 25.

Abstract

A series of pyrazoline compounds were synthesised and their osteogenic potential was explored. Out of fifteen, six compounds (3a, 4ac, 5aaa, 7, 8ab and 4aa) showed significant osteoblast differentiation in the range of 1 pM -1 μM concentrations. Amongst all, compound 4aa was identified as most active molecule which showed effective mineralisation of osteoblast cells and up regulates the osteogenic marker gene such as Bmp-2, Runx-2 and Type-1col at both transcriptional and translational level. Besides exhibiting potential osteogenic activity, 4aa also possess significant anti-apoptotic activity at 1 pM &100 pM concentration and increases the osteoblast survival in serum deprived conditions.

Keywords: Cell viability; Mineralisation; Osteoblast apoptosis; Osteoblast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation / drug effects
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Structure
  • Osteoblasts / drug effects
  • Osteogenesis / drug effects*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Pyrazoles
  • RUNX2 protein, human