Synthesis and Structure-Activity Relationship Study of 2-(amino)quinazolin-4(3<i>H</i>)-one Derivatives as Potential Inhibitors of Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA).

ABSTRACT: Background/Objectives: The rise in methicillin-resistant Staphylococcus aureus (MRSA) demands new therapeutic strategies. In this study, a series of 2-(amino)quinazolin-4(3H)-one derivatives were synthesized and evaluated for antistaphylococcal activity. Methods/Results: Through screening against S. aureus ATCC25923 and USA300 JE2, several submicromolar inhibitors were identified. Among them, compound 6l, which contains a 7-chloro substituent on the key parental scaffold, exhibited strong overall antibacterial activity (MIC₅₀: 1.0 µM, ATCC25923; 0.6 µM, JE2) and served as a lead for further structural optimization. Structure-activity relationship analysis showed that substitution at the 2-position was critical, with its optimized analog

SUBMITTER: Lee JY 

PROVIDER: S-EPMC12561453 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature