Discovery of novel steroidal pyran-oxindole hybrids as cytotoxic agents

Steroids. 2014 Oct:88:44-52. doi: 10.1016/j.steroids.2014.05.022. Epub 2014 Jun 11.

Abstract

A series of novel steroidal pyran-oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C-C and C-O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.

Keywords: Apoptosis; Cell cycle arrest; Cytotoxicity; Pyran–oxindole hybrids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Indoles / chemistry*
  • Oxindoles
  • Pyrans / chemistry*
  • Steroids / chemistry*
  • Steroids / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Indoles
  • Oxindoles
  • Pyrans
  • Steroids
  • 2-oxindole