Identification of biphenyl-based hybrid molecules able to decrease the intracellular level of Bcl-2 protein in Bcl-2 overexpressing leukemia cells

J Med Chem. 2009 Nov 12;52(21):6936-40. doi: 10.1021/jm900907s.

Abstract

With the aim of enhancing the structural complexity and diversity of an existing collection of bi- and terphenyl compounds, we synthesized hybrid molecules comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on apoptosis and differentiation, making them potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology
  • Cell Differentiation / drug effects
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Ketones / chemical synthesis*
  • Ketones / chemistry
  • Ketones / pharmacology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship
  • Terphenyl Compounds / chemical synthesis*
  • Terphenyl Compounds / chemistry
  • Terphenyl Compounds / pharmacology

Substances

  • Antineoplastic Agents
  • Biphenyl Compounds
  • Ketones
  • Proto-Oncogene Proteins c-bcl-2
  • Spiro Compounds
  • Terphenyl Compounds