Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis

Bioorg Med Chem. 2013 Apr 1;21(7):1724-34. doi: 10.1016/j.bmc.2013.01.047. Epub 2013 Jan 30.

Abstract

A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfactory selectivity against 23 kinases. The interactions of these inhibitors with RSK2 were investigated based on the proposed binding poses with molecular docking simulation. Four compounds and six compounds exhibited moderate anti-proliferation activities against PC 3 cells and MCF-7 cells, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Male
  • Molecular Docking Simulation
  • Prostatic Neoplasms / drug therapy
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors*
  • Ribosomal Protein S6 Kinases, 90-kDa / chemistry
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • indolin-2-one
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3