Search results for "010404 medicinal & biomolecular chemistry"
showing 10 items of 373 documents
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…
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…
Exploiting Cryo-EM Structural Information and All-Atom Simulations To Decrypt the Molecular Mechanism of Splicing Modulators.
2019
Splicing modulators (SMs) pladienolides, herboxidienes, and spliceostatins exert their antitumor activity by altering the ability of SF3B1 and PHF5A proteins, components of SF3b splicing factor, to recognize distinct intron branching point sequences, thus finely calibrating constitutive/alternative/aberrant splicing of pre-mRNA. Here, by exploiting structural information obtained from cryo-EM data, and by performing multiple μs-long all-atom simulations of SF3b in apo form and in complex with selected SMs, we disclose how these latter seep into the narrow slit at the SF3B1/PHF5A protein interface. This locks the intrinsic open/closed conformational transitions of SFB1's solenoidal structure…
Ethnobotanical research in Cava de' Tirreni area, Southern Italy
2019
Abstract Background To best of our knowledge, this is the first quantitative ethnobotanical study with the aim of documenting the local knowledge and practices of using plants for curing diseases in the Cava de’ Tirreni area, Salerno Province, Campania Region, Italy. The present ethnobotanical field study, carried out during 2016–2017, documents the local uses of 119 plant species for medicinal, food and domestic purposes. Methods Ethnobotanical data were documented from 70 informants: field data were collected and information on the uses of plants was gathered through semi-structured and structured interviews with persons who still retain traditional ethnobotanical knowledge. Documented da…
Bioactive Constituents of Juniperus turbinata Guss. from La Maddalena Archipelago.
2018
A comprehensive phytochemical study of Juniperus turbinata (Cupressaceae) collected from La Maddalena Archipelago (Sardinia, Italy) is reported. Both the essential oil and the ethanolic extract obtained from the aerial parts were analyzed. The essential oil appears to belong to a new chemotype compared to other Mediterranean juniper accessions, as it was favored by geographic isolation of the isles. It showed a low content of monoterpene hydrocarbons and -terpineol, ent-manoyl oxide, 1,10-di-epi-cubenol as the major constituents. The ethanolic fraction contained mainly diterpenoids. Among these, 15-formyloxyimbricatolic acid (7) is a new natural product since it has hitherto been obtained o…
Post-Translational Regulation of CYP450s Metabolism As Revealed by All-Atoms Simulations of the Aromatase Enzyme.
2019
Phosphorylation by kinases enzymes is a widespread regulatory mechanism able of rapidly altering the function of target proteins. Among these are cytochrome P450s (CYP450), a superfamily of enzymes performing the oxidation of endogenous and exogenous substrates thanks to the electron supply of a redox partner. In spite of its pivotal role, the molecular mechanism by which phosphorylation modulates CYP450s metabolism remains elusive. Here by performing microsecond-long all-atom molecular dynamics simulations, we disclose how phosphorylation regulates estrogen biosynthesis, catalyzed by the Human Aromatase (HA) enzyme. Namely, we unprecedentedly propose that HA phosphorylation at Y361 markedl…
Small molecule DNA-PK inhibitors as potential cancer therapy: a patent review (2010–present)
2021
Introduction: DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DSBs via non-homologous end joining (NHEJ). Several DNA-PK inhibitors are being investigated for potential anticancer treatment in clinical trials.Area covered: This review aims to give an overview of patents published since 2010 by analyzing the patent space and structure features of scaffolds used in those patents. It also discusses the recent clinical developments and provides perspectives on future challenges and directions in this field.Expert opinion: As a key component of the DNA damage response (DDR) pathway, DNA-PK appears to be a viable drug target for anticancer therapy. The clinical investi…
Phytochemical Constituents, Antioxidant Activity, and Toxicity Assessment of the Aerial Part Extracts from the Infraspecific Taxa of Matthiola frutic…
2021
In a project designed to investigate the specific and infraspecific taxa of Matthiola endemic to Sicily (Italy) as new potential sources of bioactive compounds in this work, the infraspecific taxa of Matthiola fruticulosa were studied, namely, subsp. fruticulosa and subsp. coronopifolia. HPLC–PDA/ESI–MS and SPME–GC/MS analyses of hydroalcoholic extracts obtained from the aerial parts of the two subspecies led to the detection of 51 phenolics and 61 volatile components, highlighting a quite different qualitative–quantitative profile. The antioxidant properties of the extracts were explored through in vitro methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and Fe2+ chelating activ…
Isolation and identification of new anthraquinones from Rhamnus alaternus L and evaluation of their free radical scavenging activity
2018
From the butanolic and the ethyl acetate extracts of Rhamnus alaternus L root bark and leaves, three new anthraquinone glycosides, alaternosides A-C (1,4,6,8 tetrahydroxy-3 methyl anthraquinone 1-O-ß-D-glucopyranosyl-4,6-di-O-α-L-rhamnopyranoside (1); 1,2,6,8 tetrahydroxy-3 methyl anthraquinone 8-O-ß-D-glucopyranoside (2) and 1, 6 dihydroxy-3 methyl 6 [2′-Me (heptoxy)] anthraquinone (3)) were isolated and elucidated together with the two known anthraquinone glycosides, Physcion-8-O-rutinoside (4) and emodin-6-O-α-L-rhamnoside (5) as well as with the known kaempferol-7-methylether (6), β-sitosterol (7) and β-sitosterol-3-O-glycoside (8). Their chemical structures were elucidated using spectr…
Cytotoxic drimane meroterpenoids from the Indonesian marine sponge Dactylospongia elegans
2017
Abstract Chemical investigation of the methanol extract of an Indonesian marine sponge Dactylospongia elegans (family Thorectidae) afforded two undescribed drimane meroterpenoidal metabolites, dactylospongenones G and H (1 and 2) together with thirteen known compounds (3–15) including pelorol, 5-epi-ilimaquinone, 5-epi-smenospongine, 5-epi-smenospongidine, nakijiquinone D, smenospongine C, isospongiaquinone, isosmenospongine, nakijiquinones A-C, G and 5-epi-nakijiquinone Q. The structures of the new metabolites were unambiguously determined by 1D and 2D NMR spectroscopy and by HRESIMS. All isolated compounds were assessed for their antimicrobial, antitubercular and cytotoxic activities. Sev…