Design, Synthesis, and Antibacterial Activity of Novel Carbacephems

Abstract

Syntheses of (±)-cis-3-hydroxycarbonyl-7-(phenylacetamido)carbacephem (10 ), (±)-cis-3-methoxycarbonyl-7-(phenylacetamido)carbacephem (11 ), (±)-cis-2-chloro-3-hydroxycarbonyl-7-(phenylacetamido)carbacephem (14 ), and (±)-cis-2-chloro-3-methoxycarbonyl-7-(phenylacetamido)carbacephem (15 ) were accomplished. These four heretofore undescribed compounds 10 , 11 , 14 , and 15 showed notable activity against Staphylococcus aureus FDA 209P, Escherichia coli ATCC 39188, Pseudomonas aeruginosa 1101-75, Klebsiella pneumoniae NCTC 418 as well as the β-lactamase producing organisms E. coli A9675, P. aeruginosa 18S-H and methicillin-resistant organism S. aureus 95. The electronic activation of lactam moieties of 11 and 15 enhanced remarkably their antibacterial activity relative to those of the 10 and 14 . The chlorine atom in 14 and 15 , acting as an effective leaving group, also resulted in an increment in the biological activity in comparison with those of the parent carbacephemes 10 and 11 . The mode of action related to 14 and 15 can be explained by a non-classical [1,4]-elimination process.

Effects of paraoxon and ethylparathion on choline oxidase from Alcaligenes species: Inhibition and denaturation

“…Also, the m-value has been used as index of the amount of protein surface exposed to the solvent upon unfolding. A similar dependence on accessible surface area has been demonstrated for heat capacity changes ( C P ) for a set of proteins [38,39]. The m-values and heat capacity changes correlate well with each other, and the C P of a protein is linearly related to the fraction of its hydrophobic residues [40,41].…”

Comparison between two different hemichromes of hemoglobins (HbA and HbS) induced by n-dodecyl trimethylammonium bromide: Chemometric study

“…Furthermore, the red shift of maximum wavelength confirms the folded state of intermediate relative to the native state indicating that a folded structure is formed. However, if the blue shift of Soret band happens, then less folded structure would form [66,67]. The absorption spectra at different concentrations of DTAB show an isosbestic point at 429 nm.…”

Dual behavior of sodium dodecyl sulfate as enhancer or suppressor of insulin aggregation and chaperone-like activity of camel αS1-casein

“…5A, column 11). The exceedingly increased ANS fluorescence intensity, as the result of decreased SDS concentration (nanomolar range), demonstrated the more significant exposure of hydrophobic sites of insulin [41,42]. The transfer of ANS from a polar to a non-polar environment led to increased fluorescence intensity and a blue shift (Fig.…”

“…At this range of SDS concentration, the interactions between insulin and SDS molecules are mainly hydrophobic, although simultaneous repulsive electrostatic interactions between negative charged groups of the protein and negative charged head group of SDS can also occur. However, at low SDS concentrations (0.1-1 M), the interactions are mainly electrostatic repulsion [41,42]. These initial interactions presumably cause insulin to unfold and expose additional hydrophobic sites to the aqueous environment.…”