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.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acinetobacter baumannii / drug effects
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Acinetobacter baumannii / physiology
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / pharmacology*
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Anti-Bacterial Agents / toxicity
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Biofilms / drug effects*
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Cell Line
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Humans
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Methicillin-Resistant Staphylococcus aureus / physiology
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Microbial Sensitivity Tests
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Molecular Structure
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Pyrimidines / chemical synthesis
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Pyrimidines / pharmacology*
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Pyrimidines / toxicity
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Quinazolinones / chemical synthesis
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Quinazolinones / pharmacology*
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Quinazolinones / toxicity
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Pyrimidines
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Quinazolinones