The synthesis and cholinesterase inhibitory activities of solasodine analogues with seven-membered F ring

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00543264" target="_blank" >RIV/61388963:_____/21:00543264 - isvavai.cz</a>

Alternative codes found

RIV/61389030:_____/21:00543264 RIV/61989592:15310/21:73604677 RIV/00216275:25310/21:39917724

Result on the web

<a href="http://doi.org/10.1016/j.jsbmb.2020.105776" target="_blank" >http://doi.org/10.1016/j.jsbmb.2020.105776</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jsbmb.2020.105776" target="_blank" >10.1016/j.jsbmb.2020.105776</a>

Result language

angličtina

Original language name

The synthesis and cholinesterase inhibitory activities of solasodine analogues with seven-membered F ring

Original language description

Solasodine analogues containing a seven-membered F ring with a nitrogen atom placed at position 22a were prepared from diosgenin or tigogenin in a four-step synthesis comprising of the simultaneous opening of the F-ring and introduction of cyanide in position 22α, activation of the 26-hydroxyl group as mesylate, nitrile reduction, and N-cyclization. Solasodine, six obtained 22a(N)-homo analogues, as well as four 26a-homosolasodine derivatives and their open-chain precursors (13 in total) were tested as potential inhibitors of acetyl- and butyryl-cholinesterases and showed activity at micromolar concentrations. The structure-activity relationship study revealed that activities against studied esterases are affected by the structure of E/F rings and the substitution pattern of ring A. The most potent compound 8 acted as non-competitive inhibitors and exerted IC50 = 8.51 μM and 7.05 μM for eeAChE and eqBChE, respectively. Molecular docking studies revealed the hydrogen bond interaction of 8 with S293 of AChE, further rings are stabilized via hydrophobic interaction (ring A) or interaction with Y341 and W286 (rings B and C). Biological experiments showed no neurotoxicity of differentiated SH-SY5Y cells. More importantly, results from neuroprotective assay based on glutamate-induced cytotoxicity revealed that most derivatives had the ability to increase the viability of differentiated SH-SY5Y cells in comparison to galantamine and lipoic acid assayed as standards. The newly synthesized solasodine analogues are able to inhibit and to bind cholinesterases in noncompetitive mode of inhibition and exhibited neuroprotection potential of differentiated neuroblastoma cells after Glu-induced toxicity.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Steroid Biochemistry and Molecular Biology

ISSN

0960-0760

e-ISSN

—

Volume of the periodical

205

Issue of the periodical within the volume

JAN

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

105776

UT code for WoS article

000598751500007

EID of the result in the Scopus database

2-s2.0-85095701860