Piperazine derivatives with potent drug moiety as efficient acetylcholinesterase, butyrylcholinesterase, and glutathione S‐transferase inhibitors

Journal of Biochemical and Molecular Toxicology, Journal Year: 2022, Volume and Issue: 37(2)

Published: Nov. 23, 2022

Cholinesterases catalyze the breakdown of neurotransmitter acetylcholine (ACh), a naturally occurring neurotransmitter, into choline and acetic acid, allowing nervous system to function properly. In human body, cholinesterases come in two types, including acetylcholinesterase (AChE; E.C.3.1.1.7) butyrylcholinesterase (BChE; E.C.3.1.1.8). Both cholinergic enzyme inhibitors are essential biochemical processes notably brain. On other hand, GSTs found all across nature principal Phase II detoxifying enzymes eukaryotes prokaryotes. Specific isozymes identified as therapeutic targets because they overexpressed various malignancies may have role genesis diseases such neurological disorders, multiple sclerosis, asthma, especially cancer cell. Piperazine chemicals many biological fascinating pharmacological properties. As result, therapeutically effective piperazine research is becoming more prominent. Half maximal inhibition concentrations (IC50 ) derivatives were ranging 4.59-6.48 µM for AChE, 4.85-8.35 BChE, 3.94-8.66 GST. Also, exhibited Ki values 8.04 ± 5.73-61.94 54.56, 0.24 0.03-32.14 16.20, 7.73 1.13-22.97 9.10 toward GST, respectively. Consequently, inhibitory properties AChE/BChE GST been compared Tacrine (for AChE BChE) Etacrynic acid GST).

Language: Английский

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Discovery of New 2-Phenylamino-3-Acyl-1,4-Naphthoquinones as Inhibitors of Cancer Cells Proliferation. Searching for Intra-cellular Targets Playing a Role in Cancer Cells Survival

Published: April 12, 2023

A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such discussed terms molecular descriptors like half-wave potentials, hydrophobicity molar refractivity. Compounds 4 11 display the highest activity against three cells, therefore, they subject to further studies. The silico prediction drug likeness, pkCSM SwissADME explorer online, shows that compound is a suitable lead molecule be developed. Furthermore, expression some key genes was studied DU-145 They include involved apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle (CDC25A), progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) inflammatory pathways (TNF). Compound displays an interesting profile because among these genes, mTOR significantly less expressed as compared control conditions. Molecular docking show has good affinity with mTOR, unraveling potential inhibitory effect on this protein. Due role metabolism, we suggest impaired cells proliferation by caused reduced (less protein)

Language: Английский

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Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival

Molecules, Journal Year: 2023, Volume and Issue: 28(11), P. 4323 - 4323

Published: May 24, 2023

A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such discussed terms molecular descriptors such as half-wave potentials, hydrophobicity molar refractivity. Compounds 4 11 displayed the highest activity against three cells therefore further investigated. The silico prediction drug likeness, pkCSM SwissADME explorer online, shows that compound is a suitable lead molecule to be developed. Moreover, expressions key genes studied DU-145 They include involved apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle (CDC25A), progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) inflammatory pathways (TNF). Compound displays an interesting profile because among these genes, mTOR was significantly less expressed compared control conditions. Molecular docking has good affinity with mTOR, unraveling potential inhibitory effect on this protein. Due role metabolism, we suggest impaired proliferation by caused reduced expression (less protein)

Language: Английский

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Synthesis, characterization, DFT and molecular docking studies of acetone O-((2,5-dichlorophenyl)sulfonyl) oxime

Physical Sciences Reviews, Journal Year: 2022, Volume and Issue: 8(11), P. 4017 - 4028

Published: April 27, 2022

Abstract Acetone O-((2,5-dichlorophenyl)sulfonyl) oxime was prepared from 2,5-dichlorophenylsulfonyl chloride and acetone using triethylamine. The compound characterized 1 H NMR 13 C spectra. Molecular docking performed with the cholinesterase enzymes. average affinity of acetylcholinesterase butyrylcholinesterase calculated at −7.46 ± 0.14 −6.70 0.00 kcal/mol, respectively. density functional theory method also used to complement experimental study. findings this work might be useful towards applications studied.

Language: Английский

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Investigation of Potential Effects of Some Indole Compounds on the Glutathione S-Transferase Enzyme

Biochemistry (Moscow), Journal Year: 2024, Volume and Issue: 89(3), P. 553 - 561

Published: March 1, 2024

Language: Английский

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