Spirooxindoles: Promising scaffolds for anticancer agents

Eur J Med Chem. 2015 Jun 5:97:673-98. doi: 10.1016/j.ejmech.2014.06.056. Epub 2014 Jun 27.

Abstract

The search for novel anticancer agents with more selectivity and lower toxicity continues to be an area of intensive investigation. The unique structural features of spirooxindoles together with diverse biological activities have made them privileged structures in new drug discovery. Among them, spiro-pyrrolidinyl oxindoles have been extensively studied as potent inhibitors of p53-MDM2 interaction, finally leading to the identification of MI-888, which could achieve rapid, complete and durable tumor regression in xenograft models of human cancer with oral administration and is in advanced preclinical research for cancer therapy. This review highlights recent progress of biologically active spirooxindoles for their anticancer potentials, mainly focusing on the discussions of SARs and modes of action. This article also aims to discuss potential further directions on the development of more potent analogues for cancer therapy.

Keywords: Cancer therapy; Oxindole; Spirooxindoles; Synthesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Drug Discovery / methods*
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Oxindoles
  • Spiro Compounds / chemistry*

Substances

  • Antineoplastic Agents
  • Indoles
  • Oxindoles
  • Spiro Compounds
  • 2-oxindole