Search results for "cki"
showing 10 items of 2390 documents
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
Analgesic Activity, Chemical Profiling and Computational Study on Chrysopogon aciculatus
2018
Present study was undertaken to evaluate the analgesic activity of the ethanol extract of Chrysopogon aciculatus. In addition to bioassays in mice, chemical profiling was done by LC-MS and GC-MS to identify phytochemicals, which were further docked on the catalytic site of COX-2 enzymes with a view to suggest the possible role of such phytoconstituents in the observed analgesic activity. Analgesic activity of C. aciculatus was evaluated by acetic acid induced writhing reflex method and hot plate technique. Phytochemical profiling was conducted using liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS). In docking studies, homology model of human C…
New Insights into the Genome Organization of Yeast Killer Viruses Based on “Atypical” Killer Strains Characterized by High-Throughput Sequencing
2017
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used to analyze some M-dsRNAs previously sequenced by traditional techniques, and new dsRNAs from atypical killer strains of Saccharomyces cerevisiae and Torulaspora delbrueckii. All dsRNAs expected to be present in a given yeast strain were reliably detected and sequenced, and the previously-known sequences were confirmed. The few discrepancies between viral variants were mostly located aro…
Structure-Based Discovery of Small Molecules Binding to RNA
2017
Ribonucleic acids (RNAs) constitute attractive drug targets. The wealth of structural information about RNAs is steadily increasing making it possible to use this information for the design of new ligands. Two methods that make heavy use of structural knowledge for ligand discovery are molecular docking and fragment screening. In molecular docking the structure of the binding site is used as a template for the design of new ligands using computational methods whereas in fragment screening biophysical methods are used for the detection of weak binding ligands which are subsequently elaborated into tighter binding molecules. In this chapter, we give an overview of both methods in the context …
Demo
2017
We present an innovative smartphone-centric tracking system for indoor and outdoor environments, based on the joint utilization of dead-reckoning and computer vision (CV) techniques. The system is explicitly designed for visually impaired people (although it could be easily generalized to other users) and it is built under the assumption that special reference signals, such as painted lines, colored tapes or tactile pavings are deployed in the environment for guiding visually impaired users along pre-defined paths. Thanks to highly optimized software, we are able to execute the CV and sensor-fusion algorithms in run-time on low power hardware such as a normal smartphone, precisely tracking …
Molecular Characterization of Coxsackievirus B5 Isolates from Sewage, Italy 2016–2017
2019
Hereby, the partial Viral Protein 1 sequences of Coxsackievirus B5 (CV-B5) from sewage samples, collected in Italy from 2016 to 2017, were compared with those available in GenBank from clinical samples. Phylogenetic analysis highlighted: (I) the predominant circulation of CV-B5 genogroup B in Italy, and (II) the presence of two new sub-genogroups.
Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning.
2021
Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2′-o-ribose methyltransferase). Supported by…
Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investi…
2016
International audience; The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)(2)]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines invitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9-methylcaffein-8-ylidene)(2)]…
Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization.
2019
Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of
Reverse screening on indicaxanthin from Opuntia ficus-indica as natural chemoactive and chemopreventive agent
2018
Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified Inositol Trisphosphate 3-Kinase (ITP3K-A), Glutamate carboxypeptidase II (GCPII), Leukotriene-A4 hydr…