Search results for "in silico"
showing 10 items of 209 documents
In silico prediction of central nervous system activity of compounds. Identification of potential pharmacophores by the TOPS–MODE approach
2004
The central nervous system (CNS) activity has been investigated by using a topological substructural molecular approach (TOPS-MODE). A discriminant analysis to classify CNS and non-CNS drugs was developed on a data set (302 compounds) of great structural variability where more than 81% (247/302) were well classified. Randic's orthogonalization procedures was carried out to allow the interpretation of the model and to avoid the collinearity among descriptors. The discriminant model was assessed by a leave-n-out (when n varies from 2 to 20) cross-validation procedure (79.94% of correct classification), an external prediction set composed by 78 CNS/non-CNS drugs (80.77% of correct classificati…
Docking and synthesis of pyrrolopyrimidodiazepinone derivatives (PPDs) and their precursors: New scaffolds for DNA-interacting agents
2007
New classes of pyrrolopyrimidodiazepinone derivatives (PPDs) and their precursors were studied in silico for their ability to form stable complex with DNA fragment. In the docking studies two binding modes can be envisaged: groove mode and intercalating mode. In the case of the best ligands the docking studies revealed a common binding mode with the chromophore intercalated between GC base pairs whereas the side chain lies close to the minor groove. Synthetic approach to the PPD ring systems is discussed.
In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity
2013
The in silico COMPARE analysis was performed on 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one, a compound with promising antiproliferative activity, previously synthetized and screened against a panel of 60 human tumor cell lines. The results evidenced that this compound matches the biological properties of Chromomycin A3 and Actinomycin D, known drugs with high DNA binding affinity. Prompted by such results, a thorough spectroscopic investigation of its DNA aqueous solutions was performed, with the aim to verify its DNA-binding properties. DNA groove-binding interaction was assigned by UV-vis spectrophotometri…
Characterization of OEBT, a LIM protein
2005
LIM Proteins have been demonstrated to play key roles in pattern formation during embryonic development, cell lineage determination, and cancer differentiation. These proteins are characterized by their conserved LIM domain, which functions as a specific protein-binding site. Recently, two new members of the LIM protein family, PRICKLE1 and PRICKLE2, were characterized in silico and demonstrated to be human orthologues of the Drosophila Prickle proteins. We report on an additional member of this protein family, over-expressed breast tumor protein (OEBT). The corresponding gene was mapped to human chromosome 6p22.31. Orthologues in mouse and rat with 72 and 54% identities on a protein level …
Investigating the in vitro catabolic fate of Enniatin B in a human gastrointestinal and colonic model
2019
Abstract Enniatin B is an emerging mycotoxin known to present biological activity because of its ionophoric characteristics. This compound has demonstrated strong in vitro cytotoxicity against different cancer cells, also at low molecular concentrations. Its natural occurrence in food commodities and feed is highly reported world-wide, but few information is available about its stability in the human gastro-intestinal tract. The present work evaluates the catabolic fate of enniatin B upon in vitro simulated digestion and colonic fermentation. LC-MS target and untargeted analysis have been performed to quantify the extent of enniatin B degradation and the formation of catabolic products. The…
CALANGO: a phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species
2023
The increasing availability of high-quality genomic, annotation and phenotypic data for different species contrasts with the lack of general software for comparative genomics that integrates these data types in a statistically sound framework in order to produce biologically meaningful knowledge. In this work, we present CALANGO (Comparative AnaLysis with ANnotation-based Genomic cOmponentes), a first-principles comparative genomics tool to search for annotation terms, such as GO terms or Pfam domain IDs, associated with a quantitative variable used to rank species data, after correcting for phylogenetic relatedness. This information can be used to annotate genomes at any level, including p…
ADME Prediction with KNIME: Development and Validation of a Publicly Available Workflow for the Prediction of Human Oral Bioavailability.
2020
In silico prediction of human oral bioavailability is a relevant tool for the selection of potential drug candidates and for the rejection of those molecules with less probability of success during the early stages of drug discovery and development. However, the high variability and complexity of oral bioavailability and the limited experimental data in the public domain have mainly restricted the development of reliable in silico models to predict this property from the chemical structure. In this study we present a KNIME automated workflow to predict human oral bioavailability of new drug and drug-like molecules based on five machine learning approaches combined into an ensemble model. Th…
Boolean Networks: A Primer
2021
Abstract Autism Spectrum Disorders (ASDs) stand out as a relevant example where omics-data approaches have been extensively and successfully employed. For instance, an outstanding outcome of the Autism Genome Project relies in the identification of biomarkers and the mapping of biological processes potentially implicated in ASDs’ pathogenesis. Several of these mapped processes are related to molecular and cellular events (e.g., synaptogenesis and synapse function, axon growth and guidance, etc.) that are required for the development of a correct neuronal connectivity. Interestingly, these data are consistent with results of brain imaging studies of some patients. Despite these remarkable pr…
Lead Discovery of SARS-CoV-2 Main Protease Inhibitors through Covalent Docking-Based Virtual Screening
2021
During almost all 2020, coronavirus disease 2019 (COVID-19) pandemic has constituted the major risk for the worldwide health and economy, propelling unprecedented efforts to discover drugs for its prevention and cure. At the end of the year, these efforts have culminated with the approval of vaccines by the American Food and Drug Administration (FDA) and the European Medicines Agency (EMA) giving new hope for the future. On the other hand, clinical data underscore the urgent need for effective drugs to treat COVID-19 patients. In this work, we embarked on a virtual screening campaign against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mpro chymotrypsin-like cysteine pro…
Rapid differentiation and in situ detection of 16 sourdough lactobacillus species by multiplex PCR.
2005
ABSTRACT A two-step multiplex PCR-based method was designed for the rapid detection of 16 species of lactobacilli known to be commonly present in sourdough. The first step of multiplex PCR was developed with a mixture of group-specific primers, while the second step included three multiplex PCR assays with a mixture of species-specific primers. Primers were derived from sequences that specify the 16S rRNA, the 16S-23S rRNA intergenic spacer region, and part of the 23S rRNA gene. The primer pairs designed were shown to exclusively amplify the targeted rrn operon fragment of the corresponding species. Due to the reliability of simultaneously identifying Lactobacillus plantarum , Lactobacillus…