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• W2801492212 abstract "8-Acetoxycycloberberine (2) with a unique skeleton was first identified to display a potent activity profile against Gram-positive bacteria, especially methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration (MIC) values of 1–8 μg/mL, suggesting a possible novel mechanism of action against bacteria. Taking 2 as the lead, 23 new 8-substituted cycloberberine (CBBR) derivatives including ether, amine, and amide were synthesized and evaluated for their antibacterial effect. The structure–activity relationship revealed that the introduction of a suitable substituent at the 8-position could greatly enhance the potency against MRSA. Among them, compounds 5d and 9e demonstrated equally effective anti-MRSA potency as lead 2, with an advantage of having a more stable pharmacokinetics feature. A preliminary mechanism study indicated that compound 9e acted upon bacteria partly through catalyzing the cleavage of bacterial DNA. Therefore, we consider that 8-substituted CBBR derivatives constitute a promising class of antibacterial agents in the treatment of MRSA infections." @default.
• W2801492212 created "2018-05-17" @default.
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• W2801492212 date "2018-04-16" @default.
• W2801492212 modified "2023-10-18" @default.
• W2801492212 title "Discovery and Development of 8-Substituted Cycloberberine Derivatives as Novel Antibacterial Agents against MRSA" @default.
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• W2801492212 doi "https://doi.org/10.1021/acsmedchemlett.8b00094" @default.
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