资料摘要
资料下载A novel series of bis-indoles derived from naturally occurring marine alkaloid 4 were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected ‘hub proteins’ in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of cis-3-4-dihydrohamacanthin B (4) bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 10b that have similar anti-MRSA activity as compound 4. Structure–activity relationship (SAR) studies were carried out on 10b and led us to discover more potent compounds such as 10c, 10d, 10k and 10m with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with minimum inhibitory concentrations (MIC) for MRSA as low as 0.5 lg/ml. Some potent PK inhibitors, such as 10b, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Dpyk::ErmR) that lacks PK activity confirmed that bactericidal activity of 10d was PK-dependant.
Thiadiazolidine 1-oxide systems for phosphine-free palladium-mediated catalysis by Biotage Initiator耐士科技
简介:We herein report several highly active catalyst systems with thiadiazolidine 1-oxides as ligands for palladium in the MizorokieHeck reaction. Excellent yields of stilbenes derived from aryl iodides and bromides have been achieved using as little as 0.00002 mol % catalyst. The ligand/palladiumsystem can be stored as a stock solution open to air at room temperature with no observable loss of activity for a period of several months.
Biotage Flash Isolera 快速制备液相色谱注意事项
简介:耐士科技作为Biotage中国区总代理,以优质的服务为您提供Biotage全系产品以及相关的技术服务。1、开机前确认自动收集机械手臂下无障碍物,试管高度低于机械手臂收集针 2、运行前确认所用流动相充足,废液瓶剩余空间充足
Biotage Isolera中低压制备快速使用手册
简介:操作步骤: 1.开机,按屏幕左下方黑色电源键 2.进入开机界面后,点击Chemistry进入操作界面 3.在”Method”页面中设定好相关参数
微波合成仪Initiatior快速使用手册
简介:耐士科技作为Biotage中国区总代理,以优质的服务为您提供Biotage全系产品以及相关的技术服务。 操作步骤: 1.开机,按屏幕左下方黑色电源键 2.进入开机界面后,点击 Organic Synthesis 进入编辑界面
氨基柱的使用与保养
简介:GRACE氨基柱可同时用于正相条件和反相条件,但是在一般情况下,正相溶剂与反相溶剂是不互溶的,在更换正反相时请先用异丙醇过渡,因为异丙醇粘度较大,因此流速建议调至0.5ml/min。 了解更多或订购产品,请致电耐士科技全国服务热线:400-188-0725
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