- Development of Membrane-Active Honokiol/Magnolol Amphiphiles as Potent Antibacterial Agents against Methicillin-Resistant Staphylococcus aureus (MRSA)
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Currently, infections caused by drug-resistant bacteria have become a new challenge in anti-infective treatment, seriously endangering public health. In our continuous effort to develop new antimicrobials, a series of novel honokiol/magnolol amphiphiles were prepared by mimicking the chemical structures and antibacterial properties of cationic antimicrobial peptides. Among them, compound 5i showed excellent antibacterial activity against Gram-positive bacteria and clinical MRSA isolates (minimum inhibitory concentrations (MICs) = 0.5-2 μg/mL) with low hemolytic and cytotoxic activities and high membrane selectivity. Moreover, 5i exhibited rapid bactericidal properties, low resistance frequency, and good capabilities of disrupting bacterial biofilms. Mechanism studies revealed that 5i destroyed bacterial cell membranes, resulting in bacterial death. Additionally, 5i displayed high biosafety and potent in vivo anti-infective potency in a murine sepsis model. Our study indicates that these honokiol/magnolol amphiphiles shed light on developing novel antibacterial agents, and 5i is a potential antibacterial candidate for combating MRSA infections.
- Bai, Li-Ping,Fu, Xiangjing,Guo, Yong,Han, Meiyue,Hou, Enhua,Liu, Jifeng,Qin, Shangshang,Wen, Tingyu,Yan, Xiaoting
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p. 12903 - 12916
(2021/09/13)
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- DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS
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Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.
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Page/Page column 64-65
(2020/02/06)
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- Optimized synthesis and indium complex formation with the bifunctional chelator NODIA-Me
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The bifunctional chelator NODIA-Me holds promise for radiopharmaceutical development. NODIA-Me is based on the macrocycle TACN (1,4,7-triazacyclononane) and incorporates two additional methylimidazole arms for metal chelation and an acetic acid residue fo
- Weinmann, Christian,Holland, Jason P.,L?ppchen, Tilman,Scherer, Harald,Maus, Stephan,Stemler, Tobias,Bohnenberger, Hendrik,Ezziddin, Samer,Kurz, Philipp,Bartholom?, Mark D.
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supporting information
p. 7503 - 7512
(2018/10/24)
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- Structure-activity relationships of 9-substituted-9-dihydroerythromycin- based motilin agonists: Optimizing for potency and safety
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A series of 9-dihydro-9-acetamido-N-desmethyl-N-isopropyl erythromycin A analogues and related derivatives was generated as motilin agonists. The compounds were optimized for potency while showing both minimal antibacterial activity and hERG inhibition. As the substituent on the amide was increased in lipophilicity the potency and hERG inhibition increased, while polar groups lowered potency, without significantly impacting hERG inhibition. The N-methyl acetamide 7a showed the optimal in vitro profile and was probed further by varying the chain length to the macrocycle as well as changing the macrocycle scaffold. 7a remained the compound with the best in vitro properties. 2009 American Chemical Society.
- Shaw, Simon J.,Chen, Yue,Zheng, Hao,Fu, Hong,Burlingame, Mark A.,Marquez, Saul,Li, Yong,Claypool, Mark,Carreras, Christopher W.,Crumb, William,Hardy, Dwight J.,Myles, David C.,Liu, Yaoquan
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supporting information; experimental part
p. 6851 - 6859
(2010/04/04)
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- Functionalizing glycine derivatives by direct C-C bond formation
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(Chemical Equation Presented) Come on glycine: Two different types of glycine derivatives are α-functionalized using cross-dehydrogenative- coupling (CDC) reactions. The method allows the efficient attachment of a malonate or aromatic alkyne group on the α-position of the glycine derivatives under very mild conditions.
- Zhao, Liang,Li, Chao-Jun
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supporting information; experimental part
p. 7075 - 7078
(2009/04/07)
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- Important role of the 3-mercaptopropionamide moiety in glutathione: Promoting effect on decomposition of the adduct of glutathione with the oxoammonium ion of TEMPO
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Cyclic voltammetry of TEMPO in aqueous 0.1 M NaOH in the presence of glutathione (GSH) or cysteine (Cys) indicated the following points: (i) Both of the thiols rapidly formed adducts 3 with oxoammonium ion 1 anodically generated from TEMPO, (ii) 3 generat
- Maeda, Hatsuo,Wu, Hong-Yan,Yamauchi, Yuji,Ohmori, Hidenobu
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p. 8338 - 8343
(2007/10/03)
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