New N -(1,3,4-thiadiazole-2-yl)acetamide derivatives as human carbonic anhydrase I and II and acetylcholinesterase inhibitors

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 19

Опубликована: Март 27, 2024

Various carbonic anhydrase (CA) enzyme isoforms are known today. In addition to the use of CA inhibitors as diuretics, antiepileptics and antiglaucoma agents, inhibition other specific was reported have clinical benefits in cancers. this study, two groups 1,3,4-thiadiazole derivatives were designed synthesized act human I II (hCA hCA II) inhibitors. The activities these compounds tested vitro evaluated silico studies. activity also against acetylcholinesterase (AChE) evaluate relation newly structures AChE. analyzed by 1H NMR,13C NMR high-resolution mass spectroscopy (HRMS). results displayed a better all than that commonly used standard drug, Acetazolamide (AAZ). showed II, except for 5b 6b. Only 6a 6c superior AChE compared agent, tacrine (THA). studies, including absorption, distribution, metabolism excretion (ADME) drug-likeness evaluation, molecular docking, dynamic simulations (MDSs) density functional theory (DFT) calculations, compatible with presented details regarding structure–activity relationship.

Язык: Английский

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Methyl benzoate derivatives: in vitro Paraoxonase 1 inhibition and in silico studies

Journal of Biochemical and Molecular Toxicology, Год журнала: 2022, Номер 36(10)

Опубликована: Июнь 16, 2022

Abstract Paraoxonase 1 (PON1) can metabolize some compounds such as aromatic carboxylic acid and unsaturated aliphatic esters, arylesters, cyclic carbonate, plucuronide drugs, carbamate insecticide classes, nerve gases, lactone compounds. Methyl benzoate has recently been shown to display potent toxicity against several insect species. In the current study, we aimed investigate effect of methyl ( 1–17 ) on PON1 activity. inhibited with K I values ranging from 25.10 ± 4.73 502.10 64.72 μM. Compound 10 (methyl 4‐amino‐2‐bromo benzoate) showed best inhibition = μM). Furthermore, using ADME‐Tox, Glide XP, MM‐GBSA tools Schrödinger Suite 2021‐4, a complete ligand–receptor interaction prediction was performed characterize benzoates ), probable binding modalities versus PON1.

Язык: Английский

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Molecular Docking Studies and the Effect of Fluorophenylthiourea Derivatives on Glutathione‐Dependent Enzymes

Chemistry & Biodiversity, Год журнала: 2022, Номер 20(1)

Опубликована: Дек. 20, 2022

Cancer is a serious problem affecting the health of all human societies. Chemotherapy refers to use drugs kill cancer or origin cancer. In past three decades, researchers have studied about proteins and their roles in production cells. Glutathione S-transferases (GSTs) are superfamily enzymes that play key role cellular detoxification, protecting against reactive electrophiles attacks, including chemotherapeutic agents. reductase (GR) an important antioxidant enzyme involved cell oxidative stress. this current study, GST GR were purified from erythrocytes using affinity chromatography. was obtained with specific activity 5.95 EU/mg protein 52.38 % yield. 4.88 74.88 The effect fluorophenylthiourea derivatives on investigated. Afterward, KI values found range 23.04±4.37 μM-59.97±13.45 μM for 7.22±1.64 μM-41.24±2.55 GST. 1-(2,6-difluorophenyl)thiourea showed best inhibition both enzymes. relationships inhibitors 3D structures explained by molecular docking studies.

Язык: Английский

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Dependence on linkers’ flexibility designed for benzenesulfonamides targeting discovery of novel hCA IX inhibitors as potent anticancer agents

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2022, Номер 37(1), С. 2765 - 2785

Опубликована: Окт. 9, 2022

Herein we reported the design and synthesis of two series comprising twenty-two benzenesulfonamides that integrate s-triazine moiety. Target compounds successfully suppressed hCA IX, with IC50 ranging from 28.6 to 871 nM. Compounds 5d, 11b, 5b, 7b were most active analogues, which inhibited IX isoform in low nanomolar range (KI = 28.6, 31.9, 33.4, 36.6 nM, respectively). Furthermore, they assessed for their cytotoxic activity against a panel 60 cancer cell lines following US-NCI protocol. According five-dose assay, 13c showed significant anticancer than 5c GI50-MID values 25.08 189.01 µM, respectively. Additionally, 13c's effects on wound healing, cycle disruption, apoptosis induction NCI-H460 cells examined. Further, docking studies combined molecular dynamic simulation stable complex high binding affinity 5d exploiting favourable H-bond lipophilic interactions.HIGHLIGHTSCarbonic anhydrase (CA) inhibitors rigid flexible linkers developed.Compound is potent CA inhibitor study (IC50: nM).Compounds displayed greatest antiproliferative towards lines.Compound exposed constructive outcomes normal lines, metastasis, healing.Molecular dynamics (MDs) was utilised mode.

Язык: Английский

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Protective effect of bromelain on some metabolic enzyme activities in tyloxapol‐induced hyperlipidemic rats

Biotechnology and Applied Biochemistry, Год журнала: 2023, Номер 71(1), С. 17 - 27

Опубликована: Сен. 25, 2023

Abstract Elevation of one or more plasma lipids, such as phospholipids, cholesterol esters, cholesterol, and triglycerides, is known hyperlipidemia. In humans experimental animals, bromelain, the primary active ingredient isolated from pineapple stems, has several positive effects, including anti‐tumor growth, anticoagulation, anti‐inflammation. Hence, purpose this study was to determine possible protective impact bromelain on some metabolic enzymes (paraoxonase‐1, glutathione S ‐transferase, reductase, sorbitol dehydrogenase [SDH], aldose reductase [AR], butyrylcholinesterase [BChE], acetylcholinesterase [AChE]), activity in heart, kidney, liver rats with tyloxapol‐induced Rats were divided into three groups: control group, HL‐control group (tyloxapol 400 mg/kg, i.p. administered group), HL+bromelain (group receiving 250 mg/kg/o.d. prior administration tyloxapol i.p.). BChE, SDH, AR enzyme activities significantly increased all tissues compared control, whereas other studied decreased. Bromelain had a regulatory effect activities. conclusion, these results prove that new mediator decreases

Язык: Английский

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