1,721,010 research outputs found
From cyclopentadiene to isoxazoline-carbocyclic nucleosides: a rapid access to biological molecules through nitrosocarbonyl chemistry
No full textA rapid access to carbocyclic nucleosides containing a fused isoxazoline ring is proposed starting from cyclopentadiene. The route involves an hetero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-O tether and elaboration of the heterocyclic aminols into nucleosides via linear construction of purine and pyrimidine heterocycles
Synthesis and evaluation of haloperidol metabolite II prodrugs as anticancer agents
No full textThe use of haloperidol metabolite II (HP-metabolite II) prodrugs is an emerging strategy in the treatment of cancer. HP-metabolite II exhibits antiproliferative properties at micromolar concentrations inducing apoptosis in different types of cancer. Thus, the application of the prodrug approach appears as a useful method leading to much more desirable pharmacokinetic and pharmacodynamic properties. Some studies have shown that the esterification of the hydroxyl group of HP-metabolite II with 4-phenylbutiric acid (4-PBA) or valproic acid enhances the anticancer therapeutic potency. The current progresses in the design, synthesis and evaluation of anticancer activity of HP metabolite II prodrugs will be discussed in this review
Hyphenated 3D-QSAR statistical model-scaffold hopping analysis for the identification of potentially potent and selective sigma-2 receptor ligands
No full textA 3D quantitative structure-activity relationship (3D-QSAR) model for predicting the Ï 2receptor affinity has been constructed with the aim of providing a useful tool for the identification, design, and optimization of novel Ï 2receptor ligands. The model has been built using a set of 500 selective Ï 2receptor ligands recovered from the sigma-2 receptor selective ligand database (S2RSLDB) and developed with the software Forge. The present model showed high statistical quality as confirmed by its robust predictive potential and satisfactory descriptive capability. The drawn up 3D map allows for a prompt visual comprehension of the electrostatic, hydrophobic, and shaping features underlying Ï 2receptor ligands interaction. A theoretic approach for the generation of new lead compounds with optimized Ï 2receptor affinity has been performed by means of scaffold hopping analysis. Obtained results further confirmed the validity of our model being some of the identified moieties have already been successfully employed in the development of potent Ï 2receptor ligands. For the first time is herein reported a 3D-QSAR model which includes a number of chemically diverse Ï 2receptor ligands and well accounts for the individual ligands affinities. These features will ensure prospectively advantageous applications to speed up the identification of new potent and selective Ï 2receptor ligands
Recent advances in drug discovery of phototherapeutic non-porphyrinic anticancer agents
No full textIn the search of novel strategies for the treatment of cancer, photodynamic therapy (PDT) has emerged as an effective, safe for repeated use, and non-invasive method. This technique involves the use of two major non-toxic components, a photosensitizer (PS) and a visible or near-infrared (NIR) light source, combined to induce cellular damage in an oxygen-dependent or -independent manner. Macrocyclic compounds, involving porphyrin and their derivatives, represent the major class of PS agents used in PDT. However, due to the drawbacks associated with these PS, like photosensitivity, dark toxicity, and low wavelength absorbance, new classes of PS appear to be needed. This review summarizes over the recent advances in drug discovery of non-porphyrinic PS suitable as anticancer therapeutics in PDT. The different compounds are grouped by chemical classes and discussed in terms of phototoxicity, together with the critical aspects of design and structure-activity relationship
Sigma-2 receptor ligands QSAR model dataset
Full text linkThe data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB) and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2) receptor ligands selective over Sigma-1 (σ1) receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together). Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included
Development of a Sigma-2 Receptor affinity filter through a Monte Carlo based QSAR analysis
No full textFor the first time in sigma-2 (σ2) receptor field, a quantitative structure–activity relationship (QSAR) model has been built using pKi values of the whole set of known selective σ2 receptor ligands (548 compounds), taken from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB) (http://www.researchdsf.unict.it/S2RSLDB/), through the Monte Carlo technique and employing the software CORAL. The model has been developed by using a large and structurally diverse set of compounds, allowing for a prediction of different populations of chemical compounds endpoint (σ2 receptor pKi). The statistical quality reached, suggested that model for pKi determination is robust and possesses a satisfactory predictive potential. The statistical quality is high for both visible and invisible sets. The screening of the FDA approved drugs, external to our dataset, suggested that sixteen compounds might be repositioned as σ2 receptor ligands (predicted pKi ≥ 8). A literature check showed that six of these compounds have already been tested for affinity at σ2 receptor and, of these, two (Flunarizine and Terbinafine) have shown an experimental σ2 receptor pKi > 7. This suggests that this QSAR model may be used as focusing screening filter in order to prospectively find or repurpose new drugs with high affinity for the σ2 receptor, and overall allowing for an enhanced hit rate respect to a random screening
Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. A comprehensive systematic review
No full textSmall molecule inhibitors of adipocyte fatty acid binding protein 4 (FABP4) have attracted interest following the recent publications of beneficial pharmacological effects of these compounds. FABP4 is predominantly expressed in macrophages and adipose tissue where it regulates fatty acids (FAs) storage and lipolysis and is an important mediator of inflammation. In the past years, hundreds FABP4 inhibitors have been synthesized for effective atherosclerosis and diabetes treatments, including derivatives of niacin, quinoxaline, aryl-quinoline, bicyclic pyridine, urea, aromatic compounds and other novel heterocyclic compounds. This review provides an overview of the synthesized and discovered molecules as adipocyte fatty acid binding protein 4 inhibitors (FABP4is) since the synthesis of the putative FABP4i, BMS309403, highlighting the interactions of the different classes of inhibitors with the targets
CO2-derived non-isocyanate polyurethanes (NIPUs) and their potential applications
Full text linkUsing CO2 as feedstock to fabricate valuable products has become essential to green and sustainable chemistry and represents a rewarding challenge. Among the noticeable routes used to convert CO2 into synthetic polymers, this review highlights the reactions concerning the cycloaddition of epoxides with CO2 in cyclic carbonate as precursors for various forms of chemical synthesis, such as polycarbonates and polyurethanes (PUs). It is a fundamental challenge in polymer production to exploit biomass and CO2 as feedstock. PUs are one of the most versatile classes of polymeric materials that exhibit excellent properties. PUs are usually synthesized by a route involving the reaction of diols with diisocyanates derived from toxic phosgene gas. Non-isocyanate-derived polyurethane (NIPU) has been produced from cyclic carbonates and diamines without isocyanate. NIPU usually displays increased chemical resistance, lower permeability, improved water absorption, and thermal stability. In this review, we report the synthesis of several NIPUs for different applications in a more environmentally friendly manner, employing CO2 as a reagent and/or fully biobased reactants
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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