scholarly journals 1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3942
Author(s):  
Dawid Maliszewski ◽  
Agnieszka Wróbel ◽  
Beata Kolesińska ◽  
Justyna Frączyk ◽  
Danuta Drozdowska
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Concentration ◽  
Colorimetric Method ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Triazine Ring ◽  
Peptide Group ◽  
Nitrogen Mustards ◽  
Ache Inhibitory Activity ◽  
Bace1 Inhibition

A series of new analogs of nitrogen mustards (4a–4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman’s colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively.

scholarly journals GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hung-Hsiang Huang ◽  
Antti Hassinen ◽  
Subha Sundaram ◽  
Andrej-Nikolai Spiess ◽  
Sakari Kellokumpu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Inhibitory Activity ◽  
Secretory Pathway ◽  
Cultured Cells ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Bimolecular Fluorescence Complementation ◽  
Invariant Chain ◽  
Fluorescent Resonance Energy Transfer ◽  
Membrane Bound

Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP-L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis.

7-O-Methylwogonin from Scutellaria baicalensis Disturbs Mitotic Progression by Inhibiting Plk1 Activity in Hep3B Cells

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 217-224 ◽  
Author(s):  
Sang-Uk Woo ◽  
Hay-Ran Jang ◽  
Young-Won Chin ◽  
Hyungshin Yim
Keyword(s):  
Inhibitory Activity ◽  
Anticancer Agent ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Mitotic Cell ◽  
Scutellaria Baicalensis ◽  
Mitotic Progression ◽  
Hep3b Cells ◽  
Bi 2536

AbstractPolo-like kinase 1, a mitotic Ser/Thr kinase, has emerged as a molecular target for the development of anticancer drugs. In this study, we found that polo-like kinase 1 activity was inhibited by 7-O-methylwogonin and related flavones, including baicalein, dihydrobaicalein, and viscidulin II, isolated from Scutellaria baicalensis. Although dihydrobaicalein exhibited the highest polo-like kinase 1 inhibitory activity among the four compounds, it also inhibited other kinases, such as vaccinia-related kinase 2 and polo-like kinase 2. Baicalein and viscidulin II also showed low selectivity to polo-like kinase 1 since they inhibited polo-like kinase 3 and polo-like kinase 2, respectively. However, 7-O-methylwogonin exhibited selective polo-like kinase 1 inhibitory activity, as evidenced from in vitro kinase assays based on fluorescence resonance energy transfer assays and ADP-Glo kinase assays. In addition, examination of mitotic morphology and immunostaining using specific antibodies for the mitotic markers, p-histone H3 and mitotic protein monoclonal 2, in Hep3B cells showed that 7-O-methylwogonin treatment increased mitotic cell populations due to inhibition of mitotic progression as a result of polo-like kinase 1 inhibition. The pattern of 7-O-methylwogonin-induced mitotic arrest was similar to that of BI 2536, a specific polo-like kinase 1 inhibitor. Thus, it was suggested that 7-O-methylwogonin disturbed mitotic progression by inhibiting polo-like kinase 1 activity. These data suggest that 7-O-methylwogonin, a polo-like kinase 1 inhibitor, may be a useful anticancer agent because of its polo-like kinase 1 selectivity and effectiveness.

scholarly journals Evaluation of Acetylcholinesterase Inhibitory Activity of Fractions from Mahonia nepalensis (Berberidaceae) Extract

2017 ◽  
Vol 33 (2) ◽  
Author(s):  
Bui Thanh Tung ◽  
Phan Ke Son ◽  
Dang Kim Thu ◽  
Nguyen Thanh Hai ◽  
Nguyen Xuan Bach ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inhibitory Activity ◽  
Colorimetric Method ◽  
Dependent Manner ◽  
Etoh Extract ◽  
Ache Inhibitors ◽  
Ache Inhibitory Activity ◽  
Etoac Fraction ◽  
Promising Source

Acetylcholinesterase (AChE) is a key target in the treatment of Alzheimer’s disease. Principal role of AChE hydrolyzes the neurotransmiter acetylcholine. Medicinal plants are the potential source of AChE inhibitors. In this study, we studied the AChE inhibitory activities of extraction  Mahonia nepalensis. This medicianl plant was extracted with ethanol 96% and subsequently fractionated with n-hexane, ethyl acetate (EtOA) and n-butanol (n-BuOH) solvents. These fractions were evaluated the AChE inhibitory activity by Ellman’s colorimetric method.  Results showed that n-BuOH fraction had the strongest AChE inhibitory activity, followed by EtOH extract and the EtOAc fraction was the weakest. The n-BuOH fraction inhibited AChE activity in a dose-dependent manner with an IC50 value of 3.38 ± 0.07 μg/mL. Detailed kinetic analysis indicated that n-BuOH fraction was mixed inhibiton type with Ki value of 3.416 ± 0.05 µg/mL. Our  data suggests that  the  Mahonia nepalensis may be  a  promising  source  of  AChE  inhibitors  for Alzheimer’s disease.

scholarly journals Comparison of Chemical Compositions of the Pepper EOs From Different Cultivars and Their AChE Inhibitory Activity

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2097146
Author(s):  
Shu-Xia Chen ◽  
Kong Yang ◽  
Jia-Yao Xiang ◽  
Osafo Raymond Kwaku ◽  
Jia-Xin Han ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Inhibitory Activity ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Black Pepper ◽  
Gas Chromatography Mass Spectrometry ◽  
Chemical Compositions ◽  
Quality Marker ◽  
The World ◽  
Ache Inhibitory Activity

Pepper is one of the most popular spices over the world and is called the King of Spices. Its essential oils (EOs) could alleviate neuronal ailments due to the inhibitory effect against acetylcholinesterase (AChE). In this study, the chemical compositions of 26 EOs prepared from white and black pepper collecting from 6 different cultivars were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 133 compounds were identified in the white and black pepper EOs. Monoterpenes and sesquiterpenes were found to be riched in these EOs, of which α-pinene, β-pinene, sabinene, 3-carene, limonene, and ( E)- β-caryophyllene were the major constituents. Most of pepper EOs showed potential AChE inhibitory activity with half-maximal inhibitory concentration (IC50) values in the range of 0.5-182.5 µg/mL. Comparison of chemical constitutes of pepper EOs from different cultivars suggested that α-pinene, β-pinene, and 3-carene with an IC50 value of 3.2, 53.3, and 2.9 µg/mL, respectively, might be used as Quality-marker (Q-marker) of pepper oil in inhibiting AChE.

Acetylcholinesterase Inhibitory Activity of Uleine from Himatanthus lancifolius

2010 ◽  
Vol 65 (7-8) ◽  
pp. 440-444 ◽  
Author(s):  
Cláudia Seidl ◽  
Beatriz L. Correia ◽  
Andréa E. M. Stinghen ◽  
Cid A. M. Santos
Keyword(s):  
Inhibitory Activity ◽  
Colorimetric Method ◽  
Indole Alkaloid ◽  
Ethyl Acetate Fraction ◽  
Primary Treatment ◽  
Huperzine A ◽  
Ache Inhibition ◽  
Ache Inhibitors ◽  
Ache Inhibitory Activity ◽  
Layer Chromatography

Application of acetylcholinesterase (AChE) inhibitors is the primary treatment for Alzheimer’s disease. Alkaloids, such as physostigmine, galanthamine, and huperzine A, play an important role as AChE inhibitors. The aim of this work was to evaluate Himatanthus lancifolius (Muell. Arg.) Woodson, a Brazilian species of Apocynaceae, and its main indole alkaloid uleine, in order to identify new AChE inhibitors. The plant fluid extract, fractions, and uleine were tested for AChE inhibitory activity using Ellman’s colorimetric method for thin-layer chromatography (TLC), 96-well microplates, and also Marston’s TLC colorimetric method. Both TLC assays showed similar results. At 5 mg/mL, the fluid extract inhibited the AChE enzyme by (50.71 ± 8.2)%. The ethyl acetate fraction exhibited the highest level of AChE inhibition, followed by the dichloromethane fraction. The isolated alkaloid uleine displayed an IC50 value of 0.45 μM.

Structural dynamics of P-type ATPase ion pumps

2019 ◽  
Vol 47 (5) ◽  
pp. 1247-1257 ◽  
Author(s):  
Mateusz Dyla ◽  
Sara Basse Hansen ◽  
Poul Nissen ◽  
Magnus Kjaergaard
Keyword(s):  
Structural Dynamics ◽  
Single Molecule ◽  
New Technologies ◽  
Atp Hydrolysis ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Time Resolved ◽  
Dynamics Simulations ◽  
Types Of Information ◽  
P Type

Abstract P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the two spatially distant processes of ion binding and ATP hydrolysis. Here, we review our current understanding of the structural dynamics of P-type ATPases, focusing primarily on Ca2+ pumps. We integrate different types of information that report on structural dynamics, primarily time-resolved fluorescence experiments including single-molecule Förster resonance energy transfer and molecular dynamics simulations, and interpret them in the framework provided by the numerous crystal structures of sarco/endoplasmic reticulum Ca2+-ATPase. We discuss the challenges in characterizing the dynamics of membrane pumps, and the likely impact of new technologies on the field.

Quantum Dot Bioconjugates as Energy Donors in Fluorescence Resonance Energy Transfer Assays

2003 ◽  
Vol 773 ◽  
Author(s):  
Aaron R. Clapp ◽  
Igor L. Medintz ◽  
J. Matthew Mauro ◽  
Hedi Mattoussi
Keyword(s):  
Energy Transfer ◽  
Quantum Dot ◽  
Organic Dyes ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Genetically Engineered ◽  
Molar Ratio ◽  
Binding Assays ◽  
Specific Sequence ◽  
Donor Acceptor

AbstractLuminescent CdSe-ZnS core-shell quantum dot (QD) bioconjugates were used as energy donors in fluorescent resonance energy transfer (FRET) binding assays. The QDs were coated with saturating amounts of genetically engineered maltose binding protein (MBP) using a noncovalent immobilization process, and Cy3 organic dyes covalently attached at a specific sequence to MBP were used as energy acceptor molecules. Energy transfer efficiency was measured as a function of the MBP-Cy3/QD molar ratio for two different donor fluorescence emissions (different QD core sizes). Apparent donor-acceptor distances were determined from these FRET studies, and the measured distances are consistent with QD-protein conjugate dimensions previously determined from structural studies.

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