scholarly journals SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors

2019 ◽  
Vol 20 (21) ◽  
pp. 5385 ◽  
Author(s):  
Andrzej Bak ◽  
Hana Pizova ◽  
Violetta Kozik ◽  
Katarina Vorcakova ◽  
Jiri Kos ◽  
...  
Keyword(s):  
Spinacia Oleracea ◽  
Photosynthetic Electron Transport ◽  
3D Qsar ◽  
Inhibitory Response ◽  
Ethyl Carbamate ◽  
Landscape Index ◽  
Spinacia Oleracea L ◽  
Property Space ◽  
Silicon Based

A set of 25 novel, silicon-based carbamate derivatives as potential acetyl- and butyrylcholinesterase (AChE/BChE) inhibitors was synthesized and characterized by their in vitro inhibition profiles and the selectivity indexes (SIs). The prepared compounds were also tested for their inhibition potential on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. In fact, some of the newly prepared molecules revealed comparable or even better inhibitory activities compared to the marketed drugs (rivastigmine or galanthamine) and commercially applied pesticide Diuron®, respectively. Generally, most compounds exhibited better inhibition potency towards AChE; however, a wider activity span was observed for BChE. Notably, benzyl N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(2-hydroxyphenyl)carbamoyl]ethyl]-carbamate (2) and benzyl N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(3-hydroxyphenyl)carbamoyl]ethyl]-carbamate (3) were characterized by fairly high selective indexes. Specifically, compound 2 was prescribed with the lowest IC50 value that corresponds quite well with galanthamine inhibition activity, while the inhibitory profiles of molecules 3 and benzyl-N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(4-hydroxyphenyl)carbamoyl]ethyl]carbamate (4) are in line with rivastigmine activity. Moreover, a structure–activity relationship (SAR)-driven similarity evaluation of the physicochemical properties for the carbamates examined appeared to have foreseen the activity cliffs using a similarity–activity landscape index for BChE inhibitory response values. The ‘indirect’ ligand-based and ‘direct’ protein-mediated in silico approaches were applied to specify electronic/steric/lipophilic factors that are potentially valid for quantitative (Q)SAR modeling of the carbamate analogues. The stochastic model validation was used to generate an ‘average’ 3D-QSAR pharmacophore pattern. Finally, the target-oriented molecular docking was employed to (re)arrange the spatial distribution of the ligand property space for BChE and photosystem II (PSII).

scholarly journals Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides

2018 ◽  
Vol 19 (8) ◽  
pp. 2318 ◽  
Author(s):  
Sarka Pospisilova ◽  
Jiri Kos ◽  
Hana Michnova ◽  
Iva Kapustikova ◽  
Tomas Strharsky ◽  
...  
Keyword(s):  
Spinacia Oleracea ◽  
Biological Activities ◽  
Cell Metabolism ◽  
Photosynthetic Electron Transport ◽  
Lethal Effect ◽  
Bipolaris Sorokiniana ◽  
Spinacia Oleracea L ◽  
Inhibitor Compounds

: A series of sixteen ring-substituted N-arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra, Fusarium avenaceum, and Bipolaris sorokiniana. Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 µM, respectively) against all four staphylococcal strains and against M. tuberculosis. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs and an ability to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin, and tetracycline). In time-kill studies, a decrease of CFU/mL of >99% after 8 h from the beginning of incubation was observed. (2E)-N-(3,5-Dichlorophenyl)- and (2E)-N-(3,4-dichlorophenyl)-3-phenylprop-2-enamide had a MIC = 27.38 µM against M. tuberculosis, while a significant decrease (22.65%) of mycobacterial cell metabolism determined by the MTT assay was observed for the 3,5-dichlorophenyl derivative. (2E)-N-(3-Fluorophenyl)- and (2E)-N-(3-methylphenyl)-3-phenylprop-2-enamide exhibited MICs = 16.58 and 33.71 µM, respectively, against B. sorokiniana. The screening of the cytotoxicity of the most effective antimicrobial compounds was performed using THP-1 cells, and these chosen compounds did not shown any significant lethal effect. The compounds were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. (2E)-N-(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC50 = 5.1 µM) was the most active PET inhibitor. Compounds with fungicide potency did not show any in vivo toxicity against Nicotiana tabacum var. Samsun. The structure–activity relationships are discussed.

scholarly journals Site-specific serine phosphorylation of spinach leaf sucrose-phosphate synthase

1992 ◽  
Vol 283 (3) ◽  
pp. 877-882 ◽  
Author(s):  
J L A Huber ◽  
S C Huber
Keyword(s):  
Okadaic Acid ◽  
Spinacia Oleracea ◽  
Sucrose Phosphate Synthase ◽  
Serine Phosphorylation ◽  
Spinacia Oleracea L ◽  
Spinach Leaf ◽  
Sucrose Phosphate ◽  
Phosphate Synthase

We recently reported [Huber, Huber & Nielsen (1989) Arch. Biochem. Biophys. 270, 681-690] that spinach (Spinacia oleracea L.) sucrose-phosphate synthase (SPS; EC 2.4.1.14) was phosphorylated in vivo when leaves were fed [32P]Pi. In vitro the enzyme was phosphorylated and inactivated by using [gamma-32P]ATP. We now report that SPS is phosphorylated both in vivo and in vitro on serine residues. The protein is phosphorylated at multiple sites both in vivo and in vitro as indicated by two-dimensional peptide maps of the immunopurified SPS protein. After being fed with radiolabel, leaves were illuminated or given mannose (which activates the enzyme), in the presence or absence of okadaic acid. Feeding okadaic acid to leaves decreased the SPS activation state in the dark and light and in leaves fed mannose. Across all the treatments, the activation state of SPS in situ was inversely related to the labelling of two phosphopeptides (designated phosphopeptides 5 and 7). These two phosphopeptides are phosphorylated when SPS is inactivated in vitro with [gamma-32P]ATP, and thus are designated as regulatory (inhibitory) sites [Huber & Huber (1991) Biochim. Biophys. Acta 1091, 393-400]. Okadaic acid increased the total 32P-labelling of SPS and in particular increased labelling of the two regulatory sites, which explains the decline in activation state. In the presence of okadaic acid, two cryptic phosphorylation sites became labelled in vivo that were not apparent in the absence of the inhibitor. Overall, the results suggest that light/dark regulation of SPS activity occurs as a result of regulatory serine phosphorylation. Multiple sites are phosphorylated in vivo, but two sites in particular appear to regulate activity and dephosphorylation of these sites in vivo is sensitive to okadaic acid.

scholarly journals Preparation and Photosynthesis-Inhibiting Activity of Novel Dihalogenated 3-Hydroxynaphthalene-2-carboxanilides

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 30
Author(s):  
Jiri Kos ◽  
Tomas Gonec ◽  
Tomas Strharsky ◽  
Michal Oravec ◽  
Josef Jampilek
Keyword(s):  
Electron Transport ◽  
Photosystem Ii ◽  
Spinacia Oleracea ◽  
Photosynthetic Electron Transport ◽  
Microwave Assisted Synthesis ◽  
Inhibiting Activity ◽  
Microwave Assisted ◽  
Spinacia Oleracea L ◽  
Wide Range

In this study, a series of nine 3-hydroxynaphthalene-2-carboxanilides, disubstituted on the anilide ring by fluorine, chlorine and bromine in various positions, was prepared by microwave-assisted synthesis and characterized. The compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was within a wide range, but rather moderate; the highest activity within the series of the compounds was observed for N-(3,5-difluorophenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 9.8 µM). The compounds were found to inhibit PET in photosystem II.

scholarly journals Synthesis and Biological Evaluation of 2-Hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(Alkoxycarbonyl)amino]benzoates

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Jan Tengler ◽  
Iva Kapustíková ◽  
Matúš Peško ◽  
Rodney Govender ◽  
Stanislava Keltošová ◽  
...  
Keyword(s):  
Electron Transport ◽  
Conformational Changes ◽  
Spinacia Oleracea ◽  
Photosynthetic Electron Transport ◽  
Thylakoid Membranes ◽  
Biological Evaluation ◽  
Mycobacterial Species ◽  
Monocytic Leukaemia ◽  
Synthesis And Biological Evaluation

A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primaryin vitroscreening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity againstM. aviumsubsp.paratuberculosisandM. intracellularethan the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleraceaL.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.

Effect of plant growth regulator combination and culture period on in vitro regeneration of spinach (Spinacia oleracea L.)

2012 ◽  
Vol 7 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Quyen Van Nguyen ◽  
Hyeon Jin Sun ◽  
Kyung Hwan Boo ◽  
Doseung Lee ◽  
Ji-Hyun Lee ◽  
...  
Keyword(s):  
Plant Growth ◽  
Growth Regulator ◽  
Plant Growth Regulator ◽  
Spinacia Oleracea ◽  
In Vitro Regeneration ◽  
Culture Period ◽  
Spinacia Oleracea L

scholarly journals Red-Light Effects Sensitized by Methylene Blue on Nitrate Reductase from Spinach (Spinacia oleracea L.) Leaves

1984 ◽  
Vol 39 (11-12) ◽  
pp. 1079-1084 ◽  
Author(s):  
S. G. Mauriño ◽  
M. A. Vargas ◽  
P. J. Aparicio ◽  
J. M. Maldonado
Keyword(s):  
Methylene Blue ◽  
Nitrate Reductase ◽  
Spinacia Oleracea ◽  
Red Light ◽  
Deuterated Water ◽  
Anaerobic Conditions ◽  
Molybdenum Complex ◽  
Spinacia Oleracea L ◽  
Light Effects

Abstract Nitrate reductase from spinach (Spinacia oleracea L.) leaves, which had been inactivated in vitro by incubation with NADH and cyanide, was fully reactivated in minutes when irradiated in anaerobic conditions with red light in the presence of methylene blue. Both the rate and the extent of reactivation increased with light intensity (6 to 100 W·m-2) and dye concentration (1 to 10 μM). On the contrary, photoreactivation was completely abolished when NADH or ethylenediaminetetra-acetic acid were present during irradiation. We propose that methylene blue, when photo excited, exhibits a redox potential positive enough to reoxidise the CN--re-duced molybdenum complex settled in the inactive enzyme, thus causing its reactivation. On the other hand, prolonged irradiation of nitrate reductase, under air and in the presence of methylene blue, promoted an oxygen-dependent irreversible inactivation of the two partial activities of the enzyme. This inactivation was markedly enhanced in 77% deuterated water and greatly prevented by azide, which indicates that singlet oxygen is the species primarily involved in the photooxidative inactivation of the enzyme.

scholarly journals Photosynthesis-Inhibiting Activity of N-(Disubstituted-phenyl)-3-hydroxynaphthalene-2-carboxamides

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4336
Author(s):  
Jiri Kos ◽  
Tomas Gonec ◽  
Michal Oravec ◽  
Izabela Jendrzejewska ◽  
Josef Jampilek
Keyword(s):  
Electron Transport ◽  
Photosystem Ii ◽  
Spinacia Oleracea ◽  
Photosynthetic Electron Transport ◽  
Inhibiting Activity ◽  
Spinacia Oleracea L ◽  
The Individual

A set of twenty-four 3-hydroxynaphthalene-2-carboxanilides, disubstituted on the anilide ring by combinations of methoxy/methyl/fluoro/chloro/bromo and ditrifluoromethyl groups at different positions, was prepared. The compounds were tested for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3,5-Difluorophenyl)-, N-(3,5-dimethylphenyl)-, N-(2,5-difluorophenyl)- and N-(2,5-dimethylphenyl)-3-hydroxynaphthalene-2-carboxamides showed the highest PET-inhibiting activity (IC50 ~ 10 µM) within the series. These compounds were able to inhibit PET in photosystem II. It has been found that PET-inhibiting activity strongly depends on the position of the individual substituents on the anilide ring and on the lipophilicity of the compounds. The electron-withdrawing properties of the substituents contribute towards the PET activity of these compounds.

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