149505-87-3Relevant articles and documents
Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents
Kuppusamy, Rajesh,Yasir, Muhammad,Berry, Thomas,Cranfield, Charles G.,Nizalapur, Shashidhar,Yee, Eugene,Kimyon, Onder,Taunk, Aditi,Ho, Kitty K.K.,Cornell, Bruce,Manefield, Mike,Willcox, Mark,Black, David StC,Kumar, Naresh
, p. 1702 - 1722 (2017/11/17)
Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3′-amino-[1,1′-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.
Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction
Jarvis, Ashley,Allerston, Charles K.,Jia, Haiyan,Herzog, Birger,Garza-Garcia, Acely,Winfield, Natalie,Ellard, Katie,Aqil, Rehan,Lynch, Rosemary,Chapman, Chris,Hartzoulakis, Basil,Nally, James,Stewart, Mark,Cheng, Lili,Menon, Malini,Tickner, Michelle,Djordjevic, Snezana,Driscoll, Paul C.,Zachary, Ian,Selwood, David L.
supporting information; experimental part, p. 2215 - 2226 (2010/08/21)
We report the molecular design and synthesis of EG00229,2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRPl) and the structural characterization of NRPl-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRPl bl domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRPl and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells was reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1.
Cyclic imino derivatives and pharmaceutical compositions containing them
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, (2008/06/13)
The invention relates to cyclic imino compounds which have, inter alia, valuable pharmacological properties, especially inhibitory effects on cell aggregation, pharmaceutical compositions which contain these compounds and processes for preparing them.