New Series of Pyrazoles and Imidazo-Pyrazoles Targeting Different Cancer and Inflammation Pathways

Molecules. 2021 Sep 22;26(19):5735. doi: 10.3390/molecules26195735.

Abstract

(1) Background: different previously synthesized pyrazoles and imidazo-pyrazoles showed interesting anti-angiogenic action, being able to interfere with ERK1/2, AKT and p38MAPK phosphorylation in different manners and with different potency; (2) Methods: here, a new small compound library, endowed with the same differently decorated chemical scaffolds, has been synthetized to obtain new agents able to inhibit different pathways involved in inflammation, cancer and human platelet aggregation. (3) Results: most of the new synthesized derivatives resulted able to block ROS production, platelet aggregation and p38MAPK phosphorylation both in platelets and Human Umbilical Vein Endothelial cells (HUVEC). This paves the way for the development of new agents with anti-angiogenic activity.

Keywords: ROS inhibition; anti-angiogenesis compounds; imidazo-pyrazoles; medicinal chemistry; p38MAPK; platelet aggregation inhibition; pyrazoles.

MeSH terms

  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Imidazoles / chemistry*
  • Phosphorylation / drug effects
  • Platelet Aggregation / drug effects
  • Pyrazoles / chemistry*
  • Reactive Oxygen Species / metabolism
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Imidazoles
  • Pyrazoles
  • Reactive Oxygen Species
  • Small Molecule Libraries
  • p38 Mitogen-Activated Protein Kinases