Search results for "Lactams"
showing 10 items of 54 documents
Asymmetric Synthesis of Spiro β-Lactamsviaa Squaramide- Catalyzed Sulfa-Michael Addition/Desymmetrization Protocol
2016
An efficient asymmetric synthesis of spirocyclohexenone β-lactams bearing three contiguous stereocenters has been achieved in moderate to good yields and high stereoselectivities. The protocol involves the combination of a squaramide-catalyzed sulfa-Michael addition under desymmetrization via a dynamic kinetic resolution of racemic 2,5-cyclohexadienones.
Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway.
2021
Abstract Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 μM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 μM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic de…
Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.
2018
Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei (T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors (Ki < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys–SOH) during crystallization. The P-glycoprotein efflux ratio was mea…
Staphylococcal cassette chromosome mec typing and mecA sequencing in methicillin-resistant staphylococci from Algeria: a highly diversified element w…
2016
Genetic mechanisms of methicillin resistance are still relevant in staphylococci. The aims of this study are to assess the possible exchanges of staphylococcal cassette chromosome mec (SCCmec) among isolates of methicillin-resistant staphylococci (MRS) and to check for known or new mutations in mecA DNA. A total of 35 MRS non-repetitive isolates were recovered, including 20 Staphylococcus haemolyticus, 7 Staphylococcus aureus, 4 Staphylococcus sciuri, 2 Staphylococcus saprophyticus and 1 isolate each of Staphylococcus xylosus and Staphylococcus lentus. Only 16 of the 35 strains were assigned to known SCCmec types: 7 SCCmec VII, 6 SCCmec IV and 3 SCCmec III, with possible horizontal transfer…
The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.
2016
IF 7.932; International audience; Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivo in two mouse GvHD models (C57BL/6 -> BALB/c and FVB/N -> Lgr5-eGFP), ex vivo in intestine organoids and in vitro in …
Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection
2019
Background and aims Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). Previously available direct-acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. Methods EXPEDITION-5 is a phase 3 study to evaluate efficacy and safety of the fixed-dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experienc…
International survey of antibiotic dosing and monitoring in adult intensive care units
2023
Background: In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. Methods: A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing…
Bioactive aristolactams from Piper umbellatum.
2007
Four alkaloids named piperumbellactams A-D (1-4) were isolated from branches of Piper umbellatum together with known N-hydroxyaristolam II (5), N-p-coumaroyl tyramine (6), 4-nerolidylcatechol (7), N-trans-feruloyltyramine, E-3-(3,4-dihydroxyphenyl)-N-2-[4-hydroxyphenylethyl]-2-propenamide, beta-amyrin, friedelin, apigenin 8-C-neohesperidoside, acacetin 6-C-beta-d-glucopyranoside, beta-sitosterol, its 3-O-beta-d-glucopyranoside and its 3-O-beta-d-[6'-dodecanoyl]-glucopyranoside. Glycosidase inhibition, antioxidant and antifungal activities of these compounds were evaluated. Compounds 1-3 showed moderate alpha-glucosidase enzyme inhibition with IC50 values 98.07+/-0.44, 43.80+/-0.56 and 29.64…
High level of intrinsic phenotypic antimicrobial resistance in enterobacteria from terrestrial wildlife in Gabonese national parks.
2021
Data on the prevalence of antibiotic resistance in Enterobacteriaceae in African wildlife are still relatively limited. The aim of this study was to estimate the prevalence of phenotypic intrinsic and acquired antimicrobial resistance of enterobacteria from several species of terrestrial wild mammals in national parks of Gabon. Colony culture and isolation were done using MacConkey agar. Isolates were identified using the VITEK 2 and MALDI-TOF methods. Antibiotic susceptibility was analysed and interpreted according to the European Committee on Antimicrobial Susceptibility Testing guidelines. The preliminary test for ESBL-producing Enterobacteriaceae was performed by replicating enterobacte…
Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60)
2013
Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 w…