Search results for "Lead compound"
showing 10 items of 29 documents
Ultralow thermal conductivity in 1D and 2D imidazolium-based lead halide perovskites
2021
Low-dimensional hybrid organic–inorganic metal halide perovskites are rapidly emerging as a fascinating sub-class of the three-dimensional parent structures, thanks to their appealing charge and thermal transport properties, paired to better chemical and thermal stabilities. Extensive investigations of the thermal behavior in these systems are of paramount relevance to understand their optoelectronic and thermoelectric applications. Herein, we present a complete thermophysical characterization of imidazolium lead iodide, (IMI)PbI3, a 1D pseudo-perovskite with chains of face-sharing octahedra, and histammonium lead iodide, (HIST)PbI4, a 2D layered perovskite with corner-sharing octahedra. Up…
3,4,5,3’,5’-pentabromo-2-(2’-hydroxybenzoyl) pyrrole: a potential lead compound as anti Gram-positive and anti biofilm agent
2005
The activity against Gram-positive bacteria of 3,4,5,3 ,5 -pentabromo-2-(2 -hydroxybenzoyl)pyrrole I, a synthetic anti-bacterial compound related to pyrrolomycins, was tested in vitro using seven reference bacterial strains and Staphylococcus epidermidis and Staphylococcus aureus preformed biofilms. Compound I was active against all strains tested, with minimum inhibitory concentration (MIC) values ranging from 0.002 to 0.097 mg/l and minimum bactericidal concentrations (MBCs) from 0.37 to 12.5 mg/l. Compound I was also active at low concentrations against preformed S. epidermidis and S. aureus biofilms.
The Repurposing of Old Drugs or Unsuccessful Lead Compounds by in Silico Approaches: New Advances and Perspectives
2015
Have you a compound in your lab, which was not successful against the designed target, or a drug that is no more attractive? The drug repurposing represents the right way to reconsider them. It can be defined as the modern and rationale approach of the traditional methods adopted in drug discovery, based on the knowledge, insight and luck, alias known as serendipity. This repurposing approach can be applied both in silico and in wet. In this review we report the molecular modeling facilities that can be of huge support in the repurposing of drugs and/or unsuccessful lead compounds. In the last decades, different methods were proposed to help the scientists in drug design and in drug repurpo…
Insight on [1,3]thiazolo[4,5-e]isoindoles as tubulin polymerization inhibitors
2021
A series of [1,3]thiazolo[4,5-e]isoindoles has been synthesized through a versatile and high yielding multistep sequence. Evaluation of the antiproliferative activity of the new compounds on the full NCI human tumor cell line panel highlighted several compounds that are able to inhibit tumor cell proliferation at micromolar-submicromolar concentrations. The most active derivative 11g was found to cause cell cycle arrest at the G2/M phase and induce apoptosis in HeLa cells, following the mitochondrial pathway, making it a lead compound for the discovery of new antimitotic drugs.
A synthetic method for diversification of the P1′ substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1′ bindin…
2007
Abstract A novel, general, and versatile method of diversification of the P1′ position in phosphinic pseudodipeptides, presumable inhibitors of proteolytic enzymes, was elaborated. The procedure was based on parallel derivatization of the amino group in the suitably protected phosphinate building blocks with appropriate alkyl and aryl halides. This synthetic strategy represents an original approach to phosphinic dipeptide chemistry. Its usefulness was confirmed by obtaining a series of P1′ modified phosphinic dipeptides, inhibitors of cytosolic leucine aminopeptidase, through computer-aided design basing on the structure of homophenylalanyl-phenylalanine analogue (hPheP[CH 2 ]Phe) bound in …
Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition.
2021
We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC…
Antiasthmatic acetophenones - an in vivo study on structure activity relationship.
1994
The recently isolated acetophenone glucoside androsin, as the major antiasthmatic principle of Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae), was used as a lead compound for detailed structure-activity relationship studies. More than 25 synthesized or commercially available acetophenones with modified substitution patterns were screened in the Plethysmographic guinea pig model using PAF and/or ovalbumin as challenging agents for the generation of bronchial constriction. Whereas the aglycones in most cases were more effective than the corresponding glycosides, substitution patterns in position 3 and 4 of the phenyl ring and the keto function attached to the phenyl ring were found to b…
Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands
2013
Abstract Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct arylation. The compound stabilizes several quadruplex DNA sequences including a human telomeric DNA and one from the promoter of the HSP90 gene, although the structure–activity relationships of the series are not obviously related to the quadruplex binding.
Bi3+doping in 1D ((CH3)3SO)PbI3: A model for defect interactions in halide perovskites
2022
The recently described monodimensional hybrid pseudo-perovskite ((CH3)3SO)PbI3 exhibits complete Pb2+/Bi3+ miscibility in the B site. Heterovalent substitution imposes that charge-compensating defects are introduced in the lattice as well. This paper reports the energetics of point defects and the interaction between charge-compensating defects that occur upon Bi3+ doping in ((CH3)3SO)PbI3. Periodic DFT simulations were employed to analyze the formation energy of Pb2+ vacancies, (CH3)3SO+ vacancies, iodide vacancies, or the insertion of interstitial iodide ions. Solid solutions with a large Bi3+ content were modeled considering different charge compensation defects (Pb2+ vacancies, (CH3)3SO…
Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors
2014
Abstract A new series of pseudopeptide boronate proteasome inhibitors (2–3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and t…