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• W2973158045 abstract "Staphylococcus aureus can survive both inside and outside of phagocytic and nonphagocytic host cells. Once in the intracellular milieu, most antibiotics have reduced ability to kill S. aureus, thus resulting in relapse of infection. Consequently, there is a need for antibacterial agents that can accumulate to lethal concentrations within host cells to clear intracellular infections. We have identified tetrahydrobenzo[a or c]phenanthridine and tetrahydrobenzo[a or c]acridine compounds, synthesized via a one-flask Povarov–Doebner operation from readily available amines, aldehydes, and cyclic ketones, as potent agents against drug-resistant S. aureus. Importantly, the tetrahydrobenzo[a or c]phenanthridine and tetrahydrobenzo[a or c]acridine compounds can accumulate in macrophage cells and reduce the burden of intracellular MRSA better than the drug of choice, vancomycin. We observed that MRSA could not develop resistance (by passage 30) against tetrahydrobenzo[a or c]acridine compound 15. Moreover, tetrahydrobenzo[c]acridine compound 15 and tetrahydrobenzo[c]phenanthridine compound 16 were nontoxic to red blood cells and were nonmutagenic. Preliminary data indicated that compound 16 reduced bacterial load (MRSA USA300) in mice (thigh infection model) to the same degree as vancomycin. These observations suggest that compounds 15 and 16 and analogues thereof could become therapeutic agents for the treatment of chronic MRSA infections." @default.
• W2973158045 created "2019-09-19" @default.
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• W2973158045 date "2019-09-12" @default.
• W2973158045 modified "2023-10-17" @default.
• W2973158045 title "Inhibitors of Intracellular Gram-Positive Bacterial Growth Synthesized via Povarov–Doebner Reactions" @default.
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• W2973158045 doi "https://doi.org/10.1021/acsinfecdis.9b00022" @default.
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• W2973158045 hasPublicationYear "2019" @default.
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