Synthesis and biofilm inhibition studies of 2-(2-amino-6-arylpyrimidin-4-yl)quinazolin-4(3H)-ones

Bioorg Med Chem Lett. 2020 Dec 1;30(23):127550. doi: 10.1016/j.bmcl.2020.127550. Epub 2020 Sep 12.

Abstract

Synthesis of novel 4(3H)-quinazolinonyl aminopyrimidine derivatives has been achieved via quinazolinonyl enones which in turn were obtained from 2-acyl-4(3H)-quinazolinone. They have been assayed for biofilm inhibition against Gram-positive (methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative bacteria (Acinetobacter baumannii). The analogues with 2,4,6-trimethoxy phenyl, 4-methylthio phenyl, and 3-bromo phenyl substituents (5h, 5j & 5k) have been shown to inhibit biofilm formation efficiently in MRSA with IC50 values of 20.7-22.4 μM). The analogues 5h and 5j have demonstrated low toxicity in human cells in vitro and can be investigated further as leads.

Keywords: 2-Acetylquinazolin-4(3H)-one; 4(3H)Quinazolinone; Aminopyrimidine; Anti-biofilm; MRSA biofilm.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / physiology
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Biofilms / drug effects*
  • Cell Line
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrimidines / chemical synthesis
  • Pyrimidines / pharmacology*
  • Pyrimidines / toxicity
  • Quinazolinones / chemical synthesis
  • Quinazolinones / pharmacology*
  • Quinazolinones / toxicity
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Pyrimidines
  • Quinazolinones