Search results for "lactam"
showing 10 items of 198 documents
Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta-peptides via nucleophilic ring-opening of beta-lactams.
2006
The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthes…
Role of Protein Flexibility in Enzymatic Catalysis: Quantum Mechanical−Molecular Mechanical Study of the Deacylation Reaction in Class A β-Lactamases
2002
We present a theoretical study of a mechanism for the hydrolysis of the acyl-enzyme complex formed by a class A beta-lactamase (TEM1) and an antibiotic (penicillanate), as a part of the process of antibiotic's inactivation by this type of enzymes. In the presented mechanism the carboxylate group of a particular residue (Glu166) activates a water molecule, accepting one of its protons, and afterward transfers this proton directly to the acylated serine residue (Ser70). In our study we employed a quantum mechanics (AM1)-molecular mechanics partition scheme (QM/MM) where all the atoms of the system were allowed to relax. For this purpose we used the GRACE procedure in which part of the system …
Computational study on hydrolysis of cefotaxime in gas phase and in aqueous solution
2012
We are presenting a theoretical study of the hydrolysis of a β-lactam antibiotic in gas phase and in aqueous solution by means of hybrid quantum mechanics/molecular mechanics potentials. After exploring the potential energy surfaces at semiempirical and density functional theory (DFT) level, potentials of mean force have been computed for the reaction in solution with hybrid PM3/TIP3P calculations and corrections with the B3LYP and M06-2X functionals. Inclusion of the full molecule of the antibiotic, Cefotaxime, in the gas phase molecular model has been demonstrated to be crucial since its carboxylate group can activate a nucleophilic water molecule. Moreover, the flexibility of the substra…
Inside the Hsp90 inhibitors binding mode through induced fit docking
2009
Abstract During the last few decades, the development of new anticancer strategies had to face the instability of many tumors, occurring when the genetic plasticity of cells produces new drug-resistant cancers. It has been shown that a chaperone protein, heat shock protein 90 (Hsp90), is one of the fundamental factors involved in the cell response to stresses, and its role in many biochemical pathways has been demonstrated. Thus, the inhibition of Hsp90 represents a new target of antitumor therapy, since it may influence many specific signaling pathways. The natural antibiotic Geldanamycin is the first Hsp90 inhibitor that has been identified. Nevertheless, more potent and water-soluble sma…
Comparative trial between the use of amoxicillin and amoxicillin clavulanate in the removal of third molars
2014
Objectives: The purpose of this study was to compare the use of amoxicillin (1g) vs amoxicillin and clavulanate (875/125mg) after extraction of retained third molars for prevention of infectious complications. Study Design: The study involved 546 patients attending for removal a retained third molar and divided in to two groups: Group 1 - amoxicillin and clavunate (875/125mg) group (n=257) and Group 2 - amoxicillin (1g) group (n=289). All patients were recalled for investigating the possibility of infection, presence of diarrhea and further analgesic intake. Results: From a total of 546 patients, the frequency of infection was 1.4%, without no statistically differences be - tween the two gr…
Asymmetric Synthesis of Spirocyclic β-Lactams through Copper-Catalyzed Kinugasa/Michael Domino Reactions
2018
The first copper-catalyzed highly chemo-, regio-, diastereo-, and enantioselective Kinugasa/Michael domino reaction for the desymmetrization of prochiral cyclohexadienones is described. In the presence of a chiral copper catalyst, alkyne-tethered cyclohexadienones couple with nitrones to generate the chiral spirocyclic lactams with excellent stereoselectivity (up to 97 % ee, >20:1 dr). The new method provides direct access to versatile highly functionalized spirocyclic β-lactams possessing four contiguous stereocenters, including one quaternary and one tetra-substituted stereocenter.
Role of the gem-Difluoro Moiety in the Tandem Ring-Closing Metathesis−Olefin Isomerization: Regioselective Preparation of Unsaturated Lactams
2006
Careful selection of the metathesis catalyst, solvent, and reaction conditions allows for the efficient and regioselective synthesis of isomeric fluorinated and nonfluorinated lactam derivatives II and III from precursor amides I through a ring-closing metathesis (RCM) reaction or a tandem RCM-isomerization protocol, respectively. The presence of the gem-difluoro moiety in the starting materials exerts a pivotal effect by directing the isomerization step, making the overall tandem transformation a regioselective process. The scope, limitations, and synthetic usefulness of this protocol are also discussed.
Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure : the DIANA study
2020
© 2020 The Author(s).
Selective Recognition of Phenazine by 2,6‐Dibutoxylnaphthalene‐Based Tetralactam Macrocycle
2019
A 2,6‐dibutoxylnaphthalene‐based tetralactam macrocycle was designed and synthesized. This macrocycle shows highly selective recognition to phenazine ‐‐ a well‐known secondary metabolite in bacteria and an emerging disinfection byproduct in drinking water. In contrast, the macrocycle shows no binding to the structurally similar dibenzo‐1,4‐dioxin. It was revealed that hydrogen bonding, π‐π and σ‐π interactions are the major driving forces between phenazine and the new tetralactam macrocycle. A perfect complementarity in electrostatic potential surfaces may explain the high selectivity. In addition, the macrocycle shows fluorescent response to phenazine, demonstrating its potential in fluore…
An international perspective on hospitalized patients with viral community-acquired pneumonia
2019
Background Who should be tested for viruses in patients with community acquired pneumonia (CAP), prevalence and risk factors for viral CAP are still debated. We evaluated the frequency of viral testing, virus prevalence, risk factors and treatment coverage with oseltamivir in patients admitted for CAP. Methods Secondary analysis of GLIMP, an international, multicenter, point-prevalence study of hospitalized adults with CAP. Testing frequency, prevalence of viral CAP and treatment with oseltamivir were assessed among patients who underwent a viral swab. Univariate and multivariate analysis was used to evaluate risk factors. Results 553 (14.9%) patients with CAP underwent nasal swab. Viral CA…