A5033053619- Molecular spectroscopy and chirality
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Computational Drug Discovery Methods
- Analytical Chemistry and Chromatography
- Fluorine in Organic Chemistry
- Heat shock proteins research
- Phenothiazines and Benzothiazines Synthesis and Activities
- ATP Synthase and ATPases Research
- Spectroscopy and Quantum Chemical Studies
- Axial and Atropisomeric Chirality Synthesis
- Click Chemistry and Applications
- Chemical Reaction Mechanisms
- Porphyrin and Phthalocyanine Chemistry
- Cancer therapeutics and mechanisms
- Synthesis and Properties of Aromatic Compounds
- thermodynamics and calorimetric analyses
- Influenza Virus Research Studies
- Crystallography and molecular interactions
- Coordination Chemistry and Organometallics
- Carbohydrate Chemistry and Synthesis
- Synthesis and Reactions of Organic Compounds
- Protein Structure and Dynamics
- Cholinesterase and Neurodegenerative Diseases
- Organic Chemistry Cycloaddition Reactions
University of Perugia
2011-2017
Institute of Cancer Research
2016-2017
Cancer Research UK
2016
Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, common cause for serious skin and soft tissues infections. A major contributor to aureus antibiotic is NorA efflux pump, which able extrude selected antibacterial drugs biocides from membrane, lowering their effective concentrations. Thus, inhibition promising challenging strategy that would allow recycling substrate antimicrobial agents. Among inhibitors,...
Influenza virus infections represent a serious concern to public health, being characterized by high morbidity and significant mortality. To date, compounds targeting the viral ion-channel M2 or neuraminidase are drugs available for treatment of influenza, but emergence drug-resistant mutants renders search novel targets their possible inhibitors major priority. Recently, we demonstrated that RNA-dependent RNA polymerase (RdRP) complex can be an optimal target protein–protein disruption...
Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using unbiased phenotypic screen to detect inhibitors HSF1 stress pathway. The probe is orally bioavailable displays efficacy in human ovarian carcinoma xenograft...
Significance The metabolism of xenobiotics is a critical aspect drug discovery; nowadays, aldehyde oxidase (AOX) has emerged as key metabolic enzyme having pivotal role in the failures several clinical candidates. lack homogenous data on possible substrates and not this represents serious limit for development an silico model prediction. Here, we present database 270 chemically diverse compounds containing aza-aromatic and/or amide moieties (susceptible to human AOX), experimentally tested...
The free energies of activation for the aryl-aryl rotation 17 biphenyl derivatives, bearing a heavy heteroatom (S, Se, Te, P, Si, Sn) as ortho substituent, have been measured by variable temperature NMR. These numbers, so called B values, represent meaningful measure steric hindrance exerted selected substituents. DFT computations match quite satisfactorily experimental barriers and ground state geometries well (determined, in two cases, X-ray diffraction). present values extend available...
The NorA efflux pump is a potential drug target for reversal of resistance to selected antibacterial agents, and recently we described indole-based inhibitor candidates. Herein report second class inhibitors derived from them but with significant differences in shape size. In particular, compounds 13 14 are very potent that they demonstrated the lowest IC50 values (2 μM) ever observed among all have evaluated.
The role played by the C*-H based modes (C* being chiral carbon atom) and large amplitude motions in vibrational absorption (VA) circular dichroism (VCD) spectra is investigated. example of an adduct dimethyl fumarate anthracene, i.e., dimethyl-(+)-(11R,12R)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylate, two deuterated isotopomers thereof specially synthesized for this goal, are considered. By comparing experimental DFT calculated undeuterated species, we demonstrate that bending,...
Aldehyde oxidase (AOX) is a molibdo-flavoenzyme that has raised great interest in recent years, since its contribution xenobiotic metabolism not always been identified before clinical trials, with consequent negative effects on the fate of new potential drugs. The fundamental role AOX metabolizing xenobiotics also due to attempt medicinal chemists stabilize candidates toward cytochrome P450 activity, which increases risk for compounds be susceptible nucleophile attack. Therefore, novel...
Vibrational circular dichroism spectra allow one to assign the absolute configuration and monitor conformational equilibria related CF3⋅⋅⋅OH hydrogen bonding of [2.2]paracyclophane with an external stereogenic carbon atom bearing CF3, OH H (see picture). Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: The publisher is responsible for...
Novel, optically pure 2-{4-methyl[2]paracyclo[2](5,8)quinolinophan-2-yl}-4-aryl/alkyloxazolines (QUIPHANOX) exhibiting both planar and central chirality have been prepared by reacting (Rp)- (Sp)-2-cyano-4-methyl[2]paracyclo[2](5,8)quinolinophane with 2-aryl/alkyl-2-aminoethanols. The reaction of each the above N,N-ligands [Ru(η(6)-p-cymene)Cl2]2 in methanol, presence either NH4PF6 or NaBPh4, gave corresponding half-sandwich [(η(6)-p-cymene)Ru(QUIPHANOX)Cl](+)Y(-), (Y(-) = PF6(-), BPh4(-)) as...
Abstract The torsional barriers of 2′‐substituted 2‐arylpyridines have been probed experimentally (by using dynamic NMR spectroscopy) and computationally density functional theory). Due to the compressibility lone pair, arylpyridines are up 4.2 kcal/mol smaller than those carba‐analogous biphenyls. Furthermore, ground states less twisted Finally, due an out‐of‐collinearity distortion, intramolecular repulsion is attenuated in both rotational transition states, syn coplanar conformer (in...
Long-range bonding interactions were evaluated using variable-temperature NMR spectroscopy and suitable 2'-CH2X-substituted phenylpyridines (X = Me, NMe2, OMe, F). It was found that the arylpyridyl rotational barriers lower when electronegative atoms bound to α carbon of 2' moiety. This effect ascribed a stabilizing interaction in transition state due lone pair heterocyclic nitrogen with carbon. Computational support for this hypothesis came from CCSD(T)/6-31+G(d) calculations. Steric...
Abstract Heat shock factor 1 (HSF1) was originally identified as a master regulator of the classical ‘cytoprotective’ heat response. However, large body evidence has now verified importance HSF1 to tumorigenesis and cancer progression. is activated by various elements state, reprogramming transcriptome in way that overlapping with, but distinct from, canonical heat-shock Also, there strong correlation between expression tumors adverse clinical outcomes. This indicates inhibition...