Synthesis, antimicrobial evaluation, and docking studies of novel 4-substituted quinazoline derivatives as DNA-gyrase inhibitors

Arch Pharm (Weinheim). 2010 Oct;343(10):570-6. doi: 10.1002/ardp.201000065.

Abstract

Quinazoline derivatives are reported to have anti-inflammatory, analgesic, antibacterial, and anticancer activities. The incorporation of "OCH₂CONH₂" (oxymethylcarbamide) at 4th position of the quinazoline ring was found to influence the biological activities of the molecules. With this rationale, some new oxadiazolyl methyloxy quinazolines, pyrazolyl acetoxy methyl quinazolines, triazolylmethyloxy quinazolines were synthesized from anthranilic acid through quinazolyl oxyacetylhydrazide intermediates. All the compounds were characterized by IR, ¹H-NMR, EI-MS, and C, H, N analyses and evaluated for their antimicrobial activity. Docking studies on the DNA-gyrase enzyme (1KZN) show their role in the antimicrobial activity of the molecules and explain the higher potency of compounds 6a, 6b, 8a, 8b based on ReRanking scores and binding poses of the molecules.

MeSH terms

  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology*
  • Bacteria / drug effects
  • DNA Gyrase / metabolism
  • Drug Resistance, Microbial
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fungi / drug effects
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / metabolism
  • Quinazolines / pharmacology*
  • Software
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*
  • ortho-Aminobenzoates / metabolism

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • Quinazolines
  • Topoisomerase II Inhibitors
  • ortho-Aminobenzoates
  • anthranilic acid
  • DNA Gyrase