scholarly journals Interactions of a small molecule configuration mimetic the interactions found in α-synuclein aggregation

2021 ◽  
Author(s):  
Marco A. Saraiva ◽  
M. Helena Florêncio
Keyword(s):  
Neurodegenerative Disorder ◽  
Peptide Bond ◽  
Spectroscopic Techniques ◽  
Model Interaction ◽  
Disordered Protein ◽  
Complex Interactions ◽  
Spectroscopic Characteristics ◽  
Conformational Alteration ◽  
Β Sheets ◽  
Intramolecular Hydrogen

Parkinson’s disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder. The aggregation of the amyloid disordered protein α-synuclein (Syn) has been implicated in the development of PD. Syn aggregation has been widely investigated but information concerning the conformational alterations in the diverse protein aggregated species at the molecular level is still scarce. To address this issue, it was here developed a comparative study involving the known parent N-acetyl-L-tyrosinamide (NAYA) compound and the Syn protein by using spectroscopic techniques. At least two different configurations of the NAYA compound were found to exist in solution. One configuration, known as the NAYA closed shape configuration, involves an amide intramolecular hydrogen-bonded interaction and was found to be a model interaction for the hydrophilic core of β-sheets, which are the most common conformational alteration found in Syn aggregated species. Since the spectroscopic techniques used herein also differentiate between tyrosyl and peptide bond groups and both NAYA and Syn possess such groups it was possible to assign these groups interactions in the β-sheets formed. This study retrieves the importance of using model compounds with spectroscopic characteristics similar to those found in proteins to access the complex interactions network existing in the amyloid aggregated species.

scholarly journals Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 656
Author(s):  
Rubina Munir ◽  
Muhammad Zia-ur-Rehman ◽  
Shahzad Murtaza ◽  
Sumera Zaib ◽  
Noman Javid ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Public Health Problem ◽  
Microwave Assisted Synthesis ◽  
Major Public Health Problem ◽  
Spectroscopic Techniques ◽  
Dual Inhibitor ◽  
Microwave Assisted ◽  
Ic50 Values

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC50 values less than 20 μM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC50 values of 9.68 and 11.59 μM, respectively. Various informative structure–activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties.

The Constituents of Naucleadiderrichii. Part III. Indole-Pyridine Alkaloids

1972 ◽  
Vol 50 (10) ◽  
pp. 1486-1495 ◽  
Author(s):  
D. G. Murray ◽  
A. Szakolcai ◽  
Stewart McLean
Keyword(s):  
Spectroscopic Techniques ◽  
The Novel ◽  
Working Hypothesis ◽  
Spectroscopic Characteristics ◽  
Form Ring

Six alkaloids isolated from the bark of Naucleadiderrichii have been shown to have structures that contain both indole and pyridine units. Because of the small amounts available of each constituent, investigation of structure has been confined mainly to the application of spectroscopic techniques; these have shown that all of these alkaloids belong to the novel indole-pyridine class, and have led us to propose structures or part structures with varying degrees of confidence for each of the alkaloids. Structure 1 was deduced for naucledine, C18H15N3O2, and confirmed by synthesis. Its spectroscopic characteristics indicate that nauclederine, C19H19N3O2, has structure 3, but this has not yet been confirmed by synthesis. Evidence is presented that nauclechine, C21H21N3O3, has part structures 6 and 7, and it is suggested that these can be incorporated in structure 8. A working hypothesis for the structure of nauclexine, C18H17N3O2, is represented by 9. Two alkaloids, ND-363C, C21H21N3O3, and ND-305B, C19H19N3O, are closely related, the latter being formally derived from the former by removal of a carbomethoxy group; each appears to exist as an equilibratible pair of isomers containing an indolic (substituted β-carboline) and a pyridine part linked together in a manner which may incorporate a spiro carbinolamine ether (as in 12) that can form ring-opened or solvated derivatives in some solvents.

Metal complex interactions with DNA

2015 ◽  
Vol 44 (8) ◽  
pp. 3505-3526 ◽  
Author(s):  
Benjamin J. Pages ◽  
Dale L. Ang ◽  
Elisé P. Wright ◽  
Janice R. Aldrich-Wright
Keyword(s):  
Transition Metal ◽  
Metal Complex ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Spectroscopic Techniques ◽  
Binding Modes ◽  
Dna Interactions ◽  
Diverse Range ◽  
Dna Structures ◽  
Complex Interactions

Increasing numbers of DNA structures are being revealed using a diverse range of transition metal complexes and biophysical spectroscopic techniques. Here we present a review of metal complex-DNA interactions in which several binding modes and DNA structural forms are explored.

scholarly journals Probing the determinants of protein stability: comparison of class A β-lactamases

1995 ◽  
Vol 308 (3) ◽  
pp. 859-864 ◽  
Author(s):  
M Vanhove ◽  
S Houba ◽  
J Lamotte-Brasseur ◽  
J M Frère
Keyword(s):  
Amino Acid ◽  
Hydrogen Bonds ◽  
Bacterial Species ◽  
Three Dimensional ◽  
Peptide Bond ◽  
Minor Role ◽  
Salt Bridges ◽  
Beta Lactamases ◽  
Class A ◽  
Intramolecular Hydrogen

Five class A beta-lactamases produced by various mesophilic bacterial species have been compared. Although closely related in primary and overall structures, these enzymes exhibit very different stabilities. In order to investigate the factors responsible for these differences, several features deduced from the amino acid composition and three-dimensional structures were studied for the five proteins. This analysis revealed that higher stability appeared to correlate with increased numbers of intramolecular hydrogen bonds and of salt bridges. By contrast, the global hydrophobicity of the protein seemed to play a relatively minor role. A strongly unfavourable balance between charged residues and the presence of a cis-peptide bond preceding a non-proline residue might also contribute to the particularly low stability of two of the enzymes.

N.M.R. studies of myelin basic protein. XII. Spectra in aqueous solution of a synthetic octapeptide encephalitogenic in the Lewis rat

1984 ◽  
Vol 37 (7) ◽  
pp. 1427 ◽  
Author(s):  
J Bremer ◽  
WJ Moore
Keyword(s):  
Aqueous Solution ◽  
Hydrogen Bonds ◽  
Synthetic Peptide ◽  
Basic Protein ◽  
Peptide Bond ◽  
Lewis Rat ◽  
Compact Structure ◽  
Linear Peptide ◽  
Temperature Dependences ◽  
Intramolecular Hydrogen

A synthetic peptide Ala-Gln-Arg-Pro-Gln-Asp-Glu-Asn encephalitogenic in the Lewis rat has been studied in aqueous solutions by 1H and 13C n.m.r. The configuration about the Arg-Pro peptide bond is > 99% trans. The temperature dependences and titration shifts of NH resonances areconsistent with occurrence of a number of intramolecular hydrogen bonds, leading to an unusually compact structure for a linear peptide in aqueous solution.

Solvent effects on the tautomeric equilibrium of 2,4-pentanedione

1982 ◽  
Vol 60 (10) ◽  
pp. 1178-1182 ◽  
Author(s):  
J. N. Spencer ◽  
Eric S. Holmboe ◽  
Mindy R. Kirshenbaum ◽  
Daniel W. Firth ◽  
Patricia B. Pinto
Keyword(s):  
Hydrogen Bond ◽  
Solvent Effects ◽  
Tautomeric Equilibrium ◽  
Spectroscopic Techniques ◽  
Hydrogen Bond Formation ◽  
Entropy Changes ◽  
Tautomeric Forms ◽  
Self Association ◽  
Enol Tautomer ◽  
Intramolecular Hydrogen

The influence of solvent on the equilibrium position of the tautomeric forms of 2,4-pentanedione was studied by calorimetric and nmr spectroscopic techniques. For solvents such as CCl4 and cyclohexane the intramolecular bond of the enol form persists and bulk solvent effects account for the equilibrium enol–keto content. In solvents such as DMSO, disruption of the intramolecular bond occurs and the percentage of enol falls due to unfavorable entropy changes. The enol intramolecular bond is disrupted by the solvents water and methanol. Enol hydrogen bond formation through self-association and with the solvent accounts for the entropy changes upon enolization in these solvents. The thermodynamic parameters for enolization in neat 2,4-pentanedione are rationalized by the disruption of the enol intramolecular hydrogen bond through consequent polymerization of the enol tautomer.

scholarly journals A New Cr3+ Electrochemical Sensor Based on ATNA/Nafion/Glassy Carbon Electrode

Materials ◽  
2020 ◽  
Vol 13 (12) ◽  
pp. 2695
Author(s):  
Reda M. El-Shishtawy ◽  
Mohammed M. Rahman ◽  
Tahir Ali Sheikh ◽  
Muhammad Nadeem Arshad ◽  
Fatimah A. M. Al-Zahrani ◽  
...  
Keyword(s):  
Electrochemical Sensor ◽  
Glassy Carbon Electrode ◽  
Glassy Carbon ◽  
Dynamic Range ◽  
Condensation Reaction ◽  
Intramolecular Hydrogen Bonding ◽  
Spectroscopic Techniques ◽  
Carbon Electrode ◽  
Heavy Metal Cations ◽  
Intramolecular Hydrogen

A new electrochemical sensor of metal cation in an aqueous solution based on homobifunctional tridentate disulfide Schiff base and named 1,1′-(-((disulfanediylbis(2,1-phenylene))bis(azaneylylidene))bis(methaneylylidene))bis(naphthalene-2-ol) (ATNA) was easily obtained quantitatively from the condensation reaction of 2-hydroxy-1-naphthaldehyde and 2-aminothiophenol, and then fully characterized by spectroscopic techniques for structure elucidation. The molecular structure of ATNA was also confirmed by a single-crystal X-ray diffraction study to reveal a new conformation in which the molecule was stabilized by the O–H…N type intramolecular hydrogen bonding interactions in both moieties. The ATNA was used as a selective electrochemical sensor for the detection of chromium ion (Cr3+). A thin film of ATNA was coated on to the flat surface of glassy carbon electrode (GCE) followed by 5 % ethanolic Nafion in order to make the modified GCE (ATNA/Nafion/GCE) as an efficient and sensitive electrochemical sensor. It was found to be very effective and selective against Cr3+ cations in the company of other intrusive heavy metal cations such as Al3+, Ce3+, Co2+, Cu2+, Ga3+, Hg2+, Mn2+, Pb2+, and Y3+. The detection limit at 3 S/N was found to be 0.013 nM for Cr3+ ions within the linear dynamic range (LDR) (0.1 nM–10.0 mM) of Cr3+ ions with r2 = 0.9579. Moreover; this work instigates a new methodology for developing the sensitive as well as selective electrochemical toxic cationic sensors in the field of environmental and health care.

Vibrational Spectroscopic Characterization and Coherent Anti-Stokes Raman Spectroscopy (CARS) Imaging of Artepillin C

2020 ◽  
Vol 74 (7) ◽  
pp. 751-757
Author(s):  
Wallance M. Pazin ◽  
Leonardo N. Furini ◽  
Vita Solovyeva ◽  
Tibebe Lemma ◽  
Rafael J. G. Rubira ◽  
...  
Keyword(s):  
Raman Scattering ◽  
Biological Systems ◽  
Spectroscopic Characterization ◽  
Spectroscopic Techniques ◽  
Spectroscopic Characteristics ◽  
Cars Microscopy ◽  
Surface Enhanced Raman ◽  
Artepillin C ◽  
Interesting Compound ◽  
Anti Stokes

In the following work, the vibrational spectroscopic characteristics of artepillin C are reported by means of Fourier transform infrared (FT-IR) and Raman spectroscopies, surface-enhanced Raman scattering (SERS), and coherent anti-Stokes Raman scattering (CARS) microscopy. Artepillin C is an interesting compound due to its pharmacological properties, including antitumor activity. It is found as the major component of Brazilian green propolis, a resinous mixture produced by bees to protect their hives against intruders. Vibrational spectroscopic techniques have shown a strong peak at 1599 cm−1, assigned to C=C stretching vibrations from the aromatic ring of artepillin C. From these data, direct visualization of artepillin C could be assessed by means of CARS microscopy, showing differences in the film hydration obtained for its neutral and deprotonated states. Raman-based methods show potential to visualize the uptake and action of artepillin C in biological systems, triggering its interaction with biological systems that are needed to understand its mechanism of action.

E/Z Isomerization of 3-Hydrazonocamphor Promoted by Coordination to Palladium or Platinum

2007 ◽  
Vol 72 (5-6) ◽  
pp. 649-665 ◽  
Author(s):  
M. Fernanda N. N. Carvalho ◽  
Ana S. D. Ferreira ◽  
João L. Ferreira da Silva ◽  
Luís F. Veiros
Keyword(s):  
Free Ligand ◽  
Intramolecular Hydrogen Bonding ◽  
Planar Geometry ◽  
Spectroscopic Techniques ◽  
X Ray Diffraction ◽  
X Ray ◽  
Square Planar ◽  
Intramolecular Hydrogen ◽  
C Nmr

3-Hydrazonocamphor, 3-(RR1NN)C10H14O (R = Me, R1 = H), undergoes intramolecular hydrogen bridging by coordination to platinum or palladium. This effect is evidenced by considerable decrease in the ν(C=O) frequency (compared to the free ligand) in the IR spectra of the complexes [MCl2L2] (M = Pd, Pt; L = 3-(RR1NN)C10H14O) as well as by the magnetic non- equivalence of the two ligands, as revealed by 13C NMR. DFT calculations indicate that coordination of 3-(Me(H)NN)C10H14O promotes E/Z isomerization of the hydrazono group of the ligand, inducing formation of intramolecular hydrogen bonding and corresponding stabilization of the complex. Characterization of the complexes [MCl2L2] (M = Pt; L: R, R1 = Me (1), R = Me, R1 = H (2) and M = Pd; L: R = Me, R1 = H (3)) was performed by analytical and spectroscopic techniques. Redox properties of the 3-hydazonocamphors and their complexes were studied by cyclic voltammetry. The structure of trans-[PtCl2{3-(Me2NN)C10H14O}2] was determined by single-crystal X-ray diffraction analysis. The complex has square-planar geometry and crystallizes in the tetragonal P43 space group.

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