(E)-2-Cyano-3-(5′-piperidin-1-yl-2,2′-bithien-5-yl)acrylic Acid: A Fluorescent Probe for Detecting Prefibrillar Oligomers
The synthesis of (E)-2-cyano-3-(5′-piperidin-1-yl-2,2′-bithien-5-yl)acrylic acid, a novel amyloid aggregation fluorescent probe, is reported. This new probe is able to monitor soluble oligomeric aggregates after 24 h, at which time Thioflavin T emission, commonly used to monitor amyloid fibril formation, remains unchanged. Atomic force microscopy, native polyacrylamide gel electrophoresis, and dynamic light scattering confirm that the earlier stages of aggregation are prefibrillar oligomeric species not possessing the amyloid structure. This new molecular scaffold expands the toolbox of fluorescent probes for the identification of prefibrillar oligomers, which is needed in studies aimed at …
New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens
The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding…
New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.
The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5- yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4- oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistan…