Novel pyrimidinone derivatives: synthesis, antitumor and antimicrobial evaluation

Chem Pharm Bull (Tokyo). 2012;60(4):521-30. doi: 10.1248/cpb.60.521.

Abstract

Starting from 6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (4a-d), a series of mono- and dialkyl derivatives 5a-j and 6a, b was synthesized. Hydrazinolysis of 4a, b, d and 5d afforded the hydrazino derivatives 7a-c which were cyclised to give the triazolopyrimidinones 8a-c and the pyrimidotriazinones 9a-c through the reaction with formic acid and chloroacetyl chloride, respectively. Most of the newly synthesized compounds were evaluated for their in-vitro antitumor activity. Compounds 6a and b displayed promising anticancer activity against leukaemia, non-small cell lung, melanoma, and renal cancer. On the other hand, all compounds prepared were screened for their in-vitro antibacterial and antifungal activities. Compounds 5h and j showed significant activity against Staphylococcus aureus, while compounds 5e, 7c and 8c displayed moderate inhibitory activity against Candida albicans.

MeSH terms

  • Anti-Infective Agents* / chemical synthesis
  • Anti-Infective Agents* / chemistry
  • Anti-Infective Agents* / pharmacology
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / pharmacology
  • Candida albicans / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Microbial Sensitivity Tests
  • Pyrimidinones* / chemical synthesis
  • Pyrimidinones* / chemistry
  • Pyrimidinones* / pharmacology
  • Staphylococcus aureus / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Pyrimidinones