期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 5, 期 7, 页码 777-781出版社
AMER CHEMICAL SOC
DOI: 10.1021/ml5001118
关键词
Drug resistance; reactive oxygen species; MRSA; superoxide radical; RecA; DNA damage
资金
- IISER Pune
- Department of Biotechnology, India [BT/PR6798/MED/29/636/2012]
- Council for Scientific and Industrial Research (CSIR)
- Department of Science and Technology (DST)
The number of cases of drug resistant Staphylococcus aureus infections is on the rise globally and new strategies to identify drug candidates with novel mechanisms of action are in urgent need. Here, we report the synthesis and evaluation of a series of benzo[b]phenanthridine-S,7,12(6H)-triones, which were designed based on redox-active natural products. We find that the in vitro inhibitory activity of 6-(prop-2-ynyl)benzo[b]phenanthridine-5,7,12(6H)-trione (If) against methicillin-resistant Staphylococcus aureus (MRSA), including a panel of patient-derived strains, is comparable or better than vancomycin. We show that the lead compound generates reactive oxygen species (ROS) in the cell, contributing to its antibacterial activity.
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