salsolinol Dotaz Zobrazit nápovědu
Catecholamine (dopamine, norepinephrine and epinephrine) synthesizing neurons are widely distributed in the brain, sympathetic ganglia and throughout peripheral organs. Results of several recent experiments clearly suggest that many of these neurons can also contain 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), a derivate of dopamine. However, direct proof of salsolinol synthesis in those neurons is still missing. The data obtained with administration of exogenous salsolinol strongly indicate that it may play an important role in catecholaminergic regulatory processes, such as the regulation of prolactin release and/or neuronal transmission in sympathetic ganglia. Several recent data have also indicated a relationship between salsolinol or its metabolites and the etiology of Parkinson's disease or neuropathology of chronic alcoholism. These seemingly different roles of salsolinol will be discussed separately, but some common features will also be highlighted. Based on all of the discussed data the existence of a “salsolinolergic” system using salsolinol as a neuromodulator, which may be present in catecholamine synthesizing neurons, is postulated.
- MeSH
- alkoholismus enzymologie etiologie metabolismus MeSH
- dopamin analogy a deriváty izolace a purifikace metabolismus MeSH
- financování vládou MeSH
- hormon uvolňující thyreotropin fyziologie sekrece MeSH
- isochinoliny chemická syntéza metabolismus MeSH
- katecholaminy izolace a purifikace metabolismus MeSH
- lidé MeSH
- nervový přenos genetika MeSH
- neurotransmiterové látky fyziologie metabolismus MeSH
- Parkinsonova nemoc enzymologie etiologie metabolismus MeSH
- Check Tag
- lidé MeSH
Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-β-d-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 μM, but this derivative suffered from cytotoxicity at higher concentrations. Both compounds modulated oxidative stress and caspase-3,7 activity, but 10 showed a superior effect comparable to the Ac-DEVD-CHO inhibitor. Interestingly, while both 4 and 10 outperformed the positive controls in blocking mitochondrial permeability transition pore opening, only 4 demonstrated potent restoration of the mitochondrial membrane potential (MMP) in the model. Derivatives 4 and 10 also showed neuroprotection in the Glu model, with 10 exhibiting the strongest oxidative stress reducing effect among the tested compounds, while the neuroprotective activity of 4 was probably due recovery of the MMP.
- MeSH
- biologické modely * MeSH
- isochinoliny antagonisté a inhibitory farmakologie MeSH
- kyselina glutamová metabolismus MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- neuroprotektivní látky chemická syntéza chemie farmakologie MeSH
- oxidační stres účinky léků MeSH
- triazoly chemie farmakologie MeSH
- triterpeny chemická syntéza chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- adrenalin krev MeSH
- hormon uvolňující thyreotropin farmakologie chemie MeSH
- isochinoliny farmakologie chemie MeSH
- krysa rodu rattus MeSH
- noradrenalin krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- faktory inhibující uvolňování prolaktinu analogy a deriváty farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- hormon uvolňující thyreotropin analogy a deriváty antagonisté a inhibitory MeSH
- isochinoliny farmakologie chemie metabolismus MeSH
- krysa rodu rattus MeSH
- laktace fyziologie MeSH
- prolaktin sekrece MeSH
- psychický stres fyziologie MeSH
- zadní lalok hypofýzy sekrece účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol-induced) and aspects of Alzheimer's disease (glutamate-induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol- and glutamate-induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase-3/7 activity.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemie MeSH
- glutamáty terapeutické užití MeSH
- lidé MeSH
- neuroprotektivní látky * farmakologie chemie MeSH
- simulace molekulového dockingu MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
