Search results for "Lead compound"
showing 10 items of 29 documents
Synthesis and biofilm formation reduction of pyrazole-4-carboxamide derivatives in some Staphylococcus aureus strains
2016
The ability of several N-phenyl-1H-pyrazole-4-carboxamide derivatives and other pyrazoles opportunely modified at the positions 3, 4 and 5, to reduce the formation of the biofilm in some Staphylococcus aureus strains (ATCC 29213, ATCC 25923 and ATCC 6538) were investigated. All the tested compounds were able, although to a different extent, to reduce the biofilm formation of the three bacterial strains considered. Among these, the 1-(2,5-dichlorophenyl)-5-methyl-N-phenyl-1H-pyrazole-4-carboxamide 14 resulted as the best inhibitor of biofilm formation showing an IC50 ranging from 2.3 to 32 μM, against all the three strains of S. aureus. Compound 14 also shows a good protective effect in vivo…
Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants
2021
Abstract Background COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. Object The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. Methods Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-…
Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents
2016
Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 µM), coupled with a lack of cytotoxicity towards mammalian cells (TC50>100 µM).
Development of peptidomimetic boronates as proteasome inhibitors.
2013
Abstract Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (β5), trypsin-like (β2) and caspase-like (β1). Most important for the development of effective antitumor agents is the inhibition of the β5 subunits. In this context, the dipeptide boronate bortezomib (Velcade ® ) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide bor…
3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates—new group of potential cardiotonic drugs
2005
Abstract 3,4- trans -4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates 6 – 11 were prepared by a Michael reaction of N -acetonylpyridinium chloride with 3-aryl-2-cyanothioacrylamides or by a one-pot three-carbon condensation of N -acetonylpyridinium chloride, aromatic aldehyde and 2-cyanothioacetamide, and their cardiotonic properties were studied. 3,4- trans -5-cyano-2-hydroxy-2-methyl-4-(3-nitrophenyl)-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolate 8 was considered as a lead compound in this series since it in vitro experiments (spontaneously beating rat atria) showed a cardiotonic activity similar to that of milrinone 2 , however compound 8 induced activity at lover co…
Enhanced nanoscopy of individual CsPbBr3 perovskite nanocrystals using dielectric sub-micrometric antennas
2020
We demonstrate an efficient, simple, and low-cost approach for enhanced nanoscopy in individual green emitting perovskite (CsPbBr3) nanocrystals via TiO2 dielectric nanoantenna. The observed three- to five-fold emission enhancement is attributed to near-field effects and emission steering promoted by the coupling between the perovskite nanocrystals and the dielectric sub-micrometric antennas. The dark-field scattering configuration is then exploited for surface-enhanced absorption measurements, showing a large increase in detection sensitivity, leading to the detection of individual nanocrystals. Due to the broadband spectral response of the Mie sub-micrometric antennas, the method can be e…
The In Silico Fischer Lock-and-Key Model: The Combined Use of Molecular Descriptors and Docking Poses for the Repurposing of Old Drugs
2019
Not always lead compound and/or derivatives are suitable for the specific biological target for which they are designed but, in some cases, discarded compounds proved to be good binders for other biological targets; therefore, drug repurposing constitute a valid alternative to avoid waste of human and financial resources. Our virtual lock-and-key methods, VLKA and Conf-VLKA, furnish a strong support to predict the efficacy of a designed drug a priori its biological evaluation, or the correct biological target for a set of the selected compounds, allowing thus the repurposing of known and unknown, active and inactive compounds.
Synthesis and evaluation of a glibenclamide glucose-conjugate: a potential new lead compound for substituted glibenclamide derivatives as islet imagi…
2007
The search for novel SUR1-ligands originates from the idea to influence the in vivo behaviour by adding new structural moieties to the glibenclamide structure while preserving its binding affinity. Important application of novel conjugates might be their use as radioactively labelled tracer probes in the non-invasive investigation of the islet mass. It is known that the imaging quality of a tracer could be improved by increasing its hydrophilicity, which leads to a reduced plasma protein binding and diminished the unspecific uptake by various organs. In this study the glucose molecule was chosen as a substitute of glibenclamide to enhance hydrophilicity. As expected glucose conjugation lead…
Tiratricol neutralizes bacterial endotoxins and reduces lipopolysaccharide-induced TNF-alpha production in the cell.
2008
Contains fulltext : 70610.pdf (Publisher’s version ) (Closed access) The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3',5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that neutralizes the toxic lipopolysaccharide.
Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity …
2009
International audience; Three series of 1-substituted-7-chloro-6-hydroxy-tetrahydroisoquinolines (1-butyl-, 1-phenyl- and 1-benzyl derivatives) were prepared to explore the influence of each of these groups at the 1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, and were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D(1) or D(2) affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure-activity relationships (SAR) of these three series of isoquin…