Anti-MRSA Flavonoids from Iraqi Citrus sinensis (L.)

Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a major global health challenge, contributing to millions of deaths annually due to antibiotic resistance. The development of new and effective antimicrobial agents is crucial to address this issue. In this study, the leaves and peels of Citrus sinensis (Rutaceae) were investigated as potential sources of anti-MRSA compounds. A bioassay-guided isolation protocol led to the identification of two polymethoxy flavones, 3-methoxynobiletin (4), sinensetin (7), and rutin 3’-methyl ether (12), which exhibited anti-MRSA activity against various strains with minimum inhibitory concentration (MIC) values ranging from 128–256 mg/mL. In addition, ten known flavonoids (1–3, 5, 6, 8, 9, 11–14) and a new flavanone glycoside, named sinensidin (10), which were not active against S. aureus. The chemical structures of all isolated compounds were determined using spectroscopic techniques, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESIMS).