Nawong BoonnakSuchada ChantraprommaKorbtham SathirakulChutima KaewpiboonMahidol UniversityPrince of Songkla UniversityThaksin University2020-10-052020-10-052020-10-15Bioorganic and Medicinal Chemistry Letters. Vol.30, No.20 (2020)146434050960894X2-s2.0-85089538372https://repository.li.mahidol.ac.th/handle/20.500.14594/58947© 2020 Elsevier Ltd Five isolated xanthones from the C. cochinchinense and G. mangostana were evaluated and tested for antibacterial activities. Isolated 4 and 5 exhibited potent anti-MRSA and P. aeruginosa activity, but showed poor pharmacokinetic properties via ADMET prediction. It led us to improve pharmacokinetic properties of 4 and 5 by partially modifying them in acidic condition yielding fourteen analogues. It was found that analogues 4b, 4d and 5b possessed proper pharmacokinetic properties, while only 4b exhibited the best anti-MRSA and P. aeruginosa activity. The SEM results indicated that 4b may interact with or damage the cell wall of MRSA and P. aeruginosa. Moreover, a combination of 4b and vancomycin exhibits synergistic effect against both MRSA and P. aeruginosa at MIC value of 4.98 (MIC = 18.75 μg/mL for 4b) and 9.52 μg/mL (MIC = 75 μg/mL for 4b), respectively.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.1016/j.bmcl.2020.127494