Search results for "Biomolecular"
showing 10 items of 507 documents
Hypnosis, Animal Magnetism, and Monstrosity in late Nineteenth Century English Literature
2019
We will explore the literary image of animal magnetism and hypnosis through the analysis of two works of fiction: the novels Richard Marsh’s The Beetle: A Mystery (1897) and Bram Stoker’s Dracula (1897). During all the 19th century and mainly at its last, many authors used animal magnetism and hypnosis in their fictional creations in an environmental or plot way, so much that Arthur Quiller-Couch, an important literary critic of the nineteenth century, spoke about the emergence of a new literary subgenre that he called “hypnotic fiction”. Starting from the idea that in this mesmeric and hypnotic fiction literature you can clearly trace differentiated stereotypes of magnetizers and hypnotist…
Structural Determinants for the Mode of Action of Imidazopyridine DS2 at δ-Containing γ-Aminobutyric Acid Type A Receptors
2021
Despite the therapeutic relevance of δ-containing γ-aminobutyric acid type A receptors (GABAARs) and the need for δ-selective compounds, the structural determinants for the mode and molecular site of action of δ-selective positive allosteric modulator imidazo[1,2-a]pyridine DS2 remain elusive. To guide the quest for insight, we synthesized a series of DS2 analogues guided by a structural receptor model. Using a fluorescence-based fluorometric imaging plate reader membrane potential assay, we found that the δ-selectivity and the pharmacological profile are severely affected by substituents in the 5-position of the imidazopyridine core scaffold. Interestingly, the 5-methyl, 5-bromo, and 5-chl…
Deciphering the Nonsense Readthrough Mechanism of Action of Ataluren: An in Silico Compared Study
2019
Ataluren was reported to suppress nonsense mutations by promoting the readthrough of premature stop codons, although its mechanism of action (MOA) is still debated. The likely interaction of Ataluren with CFTR-mRNA has been previously studied by molecular dynamics. In this work we extended the modeling of Ataluren's MOA by complementary computational approaches such as induced fit docking (IFD), quantum polarized ligand docking (QPLD), MM-GBSA free-energy calculations, and computational mutagenesis. In addition to CFTR-mRNA, this study considered other model targets implicated in the translation process, such as eukaryotic rRNA 18S, prokaryotic rRNA 16S, and eukaryotic Release Factor 1 (eRF…
Glucosylation of isatin-3-oxime followed by 2D in situ NMR in plant cells at highest magnetic field without labelling.
2001
The glucosylation of isatin-3-oxime (1) was monitored by in situ 2D 1H-13C inverse correlated gradient assisted NMR spectroscopy in plant cell suspension cultures of Rauvolfia serpentina without labelling. The applied high magnetic field of 800 MHz allowed measurements within 20 min at concentrations of 1 of 5.76 mM. Complete glucosylation of 1 occurs inside the cells within 72 hours. During this time isatin-3-oxime-glucoside (2) accumulates without further metabolism.
Novel 4-(3-phenylpropionamido), 4-(2-phenoxyacetamido) and 4-(cinnamamido) substituted benzamides bearing the pyrazole or indazole nucleus: synthesis…
2019
Based on some common structural features of known compounds interfering with p53 pathways and our previously synthesized benzamides, we synthesized new ethyl 5-(4-substituted benzamido)-1-phenyl-1H-pyrazole-4-carboxylates 26a-c, ethyl 5-(4-substituted benzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylates 27a-c and N-(1H-indazol-6-yl)-4-substituted benzamides 31a,b bearing in the 4 position of the benzamido moiety the 2-phenylpropanamido or 2-phenoxyacetamido or cinnamamido groups. A preliminary test to evaluate the antiproliferative activity against human lung carcinoma H292 cells highlighted how compound 26c showed the best activity. This last was therefore selected for further studies wi…
Indole Diterpenoids from an Endophytic Penicillium sp.
2019
A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots of the medicinal plant Zingiber officinale, yielded nine new indole diterpenoids (1-9), together with 13 known congeners (10-22). The structures of the new compounds were elucidated by 1D and 2D NMR analysis in combination with HRESIMS data. The absolute configuration of the new natural products 1, 3, and 7 was determined using the TDDFT-ECD approach and confirmed for 1 by single-crystal X-ray determination through anomalous dispersion. The isolated compounds were tested for cytotoxicity against L5178Y, A2780, J82, and HEK-293 cell lines. Compound 1 was the most active metabolite toward L5178Y ce…
Synthesis and in Vitro Evaluation of Biotinylated RG108: A High Affinity Compound for Studying Binding Interactions with Human DNA Methyltransferases
2006
Small-molecule inhibitors of DNA methyltransferases such as RG108 represent promising candidates for cancer drug development. We report the synthesis and in vitro analysis of a biotinylated RG108 conjugate, 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(5-[3-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)pentanoylamino]propoxy]-1H-indol-3-yl)propionic acid (bio-RG108), for the evaluation of interactions with DNA methyltransferase enzymes. The structural design of the chemically modified inhibitor was aided by molecular modeling, which suggested the possibility for extensive chemical modifications at the 5-position of the tryptophan moiety in RG108. The inhibitory activity of the corresponding d…
Porphyrin and phthalocyanine photosensitizers designed for targeted photodynamic therapy of colorectal cancer
2020
Colorectal cancer is of particular concern due to its high mortality rate count. Recent investigations on targeted phototherapy involving novel photosensitizers and drug-delivery systems have provided promising results and realistic prospects for a successful medical treatment. New research trends have been focused particularly on development of advanced molecular systems offering effective photoactive species which could be selectively delivered directly into the affected cells. Porphyrins and phthalocyanines have been considered extremely attractive for this purpose due to their molecular versatility, excellent photochemical properties and multifunctional nature. In this review it has bee…
Dispersion from C
2019
Resonance assignment of intrinsically disordered proteins is remarkably challenging due to scant chemical shift dispersion arising from conformational heterogeneity. The challenge is even greater if repeating segments are present in the amino acid sequence. To forward unambiguous resonance assignment of intrinsically disordered proteins, we present iHACANCO, HACACON and (HACA)CONCAHA, three Hα-detected 4D experiments with Cα as an additional dimension. In addition, we present (HACA)CON(CA)NH and (HACA)N(CA)CONH, new 4D Hα-start, HN-detect experiments which have two NH dimensions to enhance peak dispersion in a sequential walk through C′, NH and HN, and provide more accurate NH/HN chemical s…
Soft Nanoonions: A Dynamic Overview onto Catanionic Vesicles Temperature-Driven Transition.
2020
Catanionic vesicles are emerging interesting structures for bioapplications. They self-generate by a pairing of oppositely charged ionic surfactants that assemble into hollow structures. Specifically, the anionic-cationic surfactant pair assumes a double-tailed zwitterionic behavior. In this work, the multilamellar-to-unilamellar thermal transition of several mixed aqueous systems, with a slight excess of the anionic one, were investigated. Interestingly, it was found that the anionic counterion underwent a dissociation as a consequence of a temperature increase, leading to the mentioned thermal transition. The present work proposed the spectroscopic techniques, specifically multinuclear NM…