Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones

Eur J Med Chem. 2011 Aug;46(8):3274-81. doi: 10.1016/j.ejmech.2011.04.048. Epub 2011 May 5.

Abstract

A series of conformationally flexible and restricted dimers of monastrol as well as related dihydropyrimidones have been synthesized by employing one-pot Biginelli multicomponent reaction. These dimers have been evaluated for cytotoxic potency against selected human cancer cell lines and some of the compounds have exhibited more cytotoxic potency than the parent monastrol. Further, the DNA binding ability by thermal denaturation studies and antimicrobial activities of these compounds are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • DNA / metabolism
  • Differential Thermal Analysis
  • Dimerization
  • Drug Screening Assays, Antitumor
  • Female
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / growth & development
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Pyrimidines / pharmacology
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / pharmacology*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Structure-Activity Relationship
  • Thiones / pharmacology

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Pyrimidines
  • Pyrimidinones
  • Thiones
  • monastrol
  • DNA
  • calf thymus DNA