Synthesis and anticancer activity of (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purines

ChemMedChem. 2008 Jan;3(1):127-35. doi: 10.1002/cmdc.200700180.

Abstract

A series of eleven 2- and 6-substituted (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives was obtained by applying a standard Mitsunobu protocol that led to a six-membered ring contraction from (R,S)-3,4-dihydro-2H-1,5-benzoxathiepin-3-ol via an episulfonium intermediate. The signal approximately delta=151 ppm, which corresponds to the C4' carbon atom, is unequivocal proof of the N9' regioisomer. The potential of the target molecules as anticancer agents is reflected in their activity against the MCF-7 cancer cell line. The most active compounds have IC(50) values of (6.18+/-1.70) and (8.97+/-0.83) microM. The results indicate that the anticancer activity for the most active compounds is correlated with their capacity to induce apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Crystallography, X-Ray
  • Female
  • Heterocyclic Compounds / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Nitrogen / chemistry
  • Oxathiins / chemical synthesis
  • Oxathiins / pharmacology
  • Oxathiins / therapeutic use*
  • Purines / chemical synthesis
  • Purines / pharmacology
  • Purines / therapeutic use*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Oxathiins
  • Purines
  • Nitrogen