1318208-92-2Relevant articles and documents
Cystobactamid 507: Concise Synthesis, Mode of Action, and Optimization toward More Potent Antibiotics
Elgaher, Walid A. M.,Hamed, Mostafa M.,Baumann, Sascha,Herrmann, Jennifer,Siebenbürger, Lorenz,Krull, Jana,Cirnski, Katarina,Kirschning, Andreas,Br?nstrup, Mark,Müller, Rolf,Hartmann, Rolf W.
, p. 7219 - 7225 (2020/05/08)
Lack of new antibiotics and increasing antimicrobial resistance are among the main concerns of healthcare communities nowadays, and these concerns necessitate the search for novel antibacterial agents. Recently, we discovered the cystobactamids—a novel natural class of antibiotics with broad-spectrum antibacterial activity. In this work, we describe 1) a concise total synthesis of cystobactamid 507, 2) the identification of the bioactive conformation using noncovalently bonded rigid analogues, and 3) the first structure–activity relationship (SAR) study for cystobactamid 507 leading to new analogues with high metabolic stability, superior topoisomerase IIA inhibition, antibacterial activity and, importantly, stability toward the resistant factor AlbD. Deeper insight into the mode of action revealed that the cystobactamids employ DNA minor-groove binding as part of the drug–target interaction without showing significant intercalation. By designing a new analogue of cystobactamid 919-2, we finally demonstrated that these findings could be further exploited to obtain more potent hexapeptides against Gram-negative bacteria.
Hydrophobic side-chain interactions in a family of dimeric amide foldamers-potential alpha-helix mimetics
Kulikov, Oleg V.,Incarvito, Christopher,Hamilton, Andrew D.
supporting information; experimental part, p. 3705 - 3709 (2011/08/06)
A series of new alpha-helix mimetics based on a benzamide scaffold and potentially able to disrupt protein-protein interactions have been synthesized and characterized by X-ray analysis. Inspection of the solid state structures of aromatic amide dimers co
