Evaluation of novel multifunctional organoselenium compounds as potential cholinesterase inhibitors against Alzheimer’s disease

Medicinal Chemistry Research, Journal Year: 2022, Volume and Issue: 31(6), P. 894 - 904

Published: April 12, 2022

Language: Английский

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IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 18

Published: March 22, 2022

Glioblastoma multiforme (GBM) is a notably lethal brain tumor associated with high proliferation rate and therapeutic resistance, while currently effective treatment options are still lacking. Imidazo[1,2-a]pyridine derivatives organoselenium compounds largely used in medicinal chemistry drug development. This study aimed at further investigating the antitumor mechanism of IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine), selenylated imidazo[1,2-a]pyridine derivative glioblastoma cells. exhibited cytotoxicity against A172 cells ( I C 50 = 1.8 μ M ) selectivity for this cell. The compound has pharmacological properties verified its ADMET profile, especially related to blood-brain barrier (BBB) permeability. At low concentration (1 μM), induced intracellular redox state modulation depletion TrxR GSH levels as well inhibition NRF2 protein. also decreased mitochondrial membrane potential, cytochrome c release, chromatin condensation. Furthermore, apoptosis by decreasing Bcl-xL increasing γ-H2AX p53 proteins. Treatment cell cycle arrest showed antiproliferative effect Akt/mTOR/HIF-1α ERK 1/2 signaling pathways. In addition, displayed significant p38 MAPK p-p38, leading inflammasome complex proteins (NLRP3 caspase-1) These collective findings demonstrated that bioactive molecule can be considered candidate development novel treatment.

Language: Английский

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Novel Organoselenium Redox Modulators with Potential Anticancer, Antimicrobial, and Antioxidant Activities

Antioxidants, Journal Year: 2022, Volume and Issue: 11(7), P. 1231 - 1231

Published: June 23, 2022

Novel organic selenides were developed in good yields (up to 91%), and their chemical entities confirmed by IR, MS, 1H- 13C-NMR spectroscopy. Their anticancer antimicrobial properties estimated against different human cancer (MCF-7 HepG2) healthy (WI-38) cell lines, as well several microbial strains (Escherichia coli, Staphylococcus aureus, Candida albicans). Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) bioassays used for estimation of antioxidant activities. Generally, cytotoxicity results more pronounced MCF-7 cells than HepG2 cells. Compound 2-((4-((1-hydroxynaphthalen-2-yl)diazenyl)phenyl)selanyl)-N-phenylacetamide (9) was most cytotoxic, even doxorubicin, with IC50 3.27 ± 0.2 4.17 µM twelve-times selective, respectively. Interestingly, compound 9 exhibited similar potential reference antibacterial antifungal drugs comparable activity vitamin C. These point selective interesting some newly synthesized selenides, which turn needs further vitro studies.

Language: Английский

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Organosulphur and organoselenium compounds as emerging building blocks for catalytic systems forO-arylation of phenols, a C–O coupling reaction

Dalton Transactions, Journal Year: 2022, Volume and Issue: 51(21), P. 8103 - 8132

Published: Jan. 1, 2022

Diaryl ethers form an important class of organic compounds.

Language: Английский

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Role of Sulphur and Heavier Chalcogens on the Antioxidant Power and Bioactivity of Natural Phenolic Compounds

Biomolecules, Journal Year: 2022, Volume and Issue: 12(1), P. 90 - 90

Published: Jan. 6, 2022

The activity of natural phenols is primarily associated to their antioxidant potential, but ultimately expressed in a variety biological effects. Molecular scaffold manipulation this large compounds currently pursued approach boost or modulate properties. Insertion S/Se/Te containing substituents on may increase/decrease H-donor/acceptor ability by electronic and stereo-electronic effects related the site substitution geometrical constrains. Oxygen sulphur/selenium isosteric replacement resveratrol ferulic acid leads an increase radical scavenging with respect parent phenol. Several chalcogen-substituted inspired Vitamin E flavonoids have been prepared, which some cases prove be chain-breaking antioxidants, far better than counterparts. Conjugation catechols thiols (cysteine, glutathione, dihydrolipoic acid) easily achieved addition corresponding ortho-quinones. Noticeable examples potentiated activities are human metabolite 5-S-cysteinyldopa, high iron-induced lipid peroxidation inhibitory activity, due strong iron (III) binding, 5-S-glutathionylpiceatannol most effective inhibitor nitrosation processes, 5-S-lipoylhydroxytyrosol, its polysulfides that proved valuable oxidative-stress protective agents various cellular models. Different methodologies used for evaluation power these against compounds. These include kinetics inhibition alkylperoxyl radicals, common chemical assays scavenging, OH• mediated hydroxylation/oxidation model systems, ferric- copper-reducing power, nitrosating species. In addition, computational methods allowed researchers determine Bond Dissociation Enthalpy values OH groups chalcogen modified phenolics predict best performing derivative. Finally, Se Te as mimic glutathione peroxidase has evaluated, together other including anticancer action (neuro)protective achievements discussed rationalized guide future development field.

Language: Английский

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