Intracellular distribution of new tacrine analogues as a potential cause of their cytotoxicity against human neuroblastoma cells SH-SY5Y

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F18%3A10380469" target="_blank" >RIV/00179906:_____/18:10380469 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1007/s00044-018-2241-6" target="_blank" >http://dx.doi.org/10.1007/s00044-018-2241-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00044-018-2241-6" target="_blank" >10.1007/s00044-018-2241-6</a>

Result language

angličtina

Original language name

Intracellular distribution of new tacrine analogues as a potential cause of their cytotoxicity against human neuroblastoma cells SH-SY5Y

Original language description

Four new glyco-conjugated tacrine derivatives, 4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl)-1-(1,2,3,4-tetrahydroacridin-9-yl)thiosemicarbazide (1), 4-(2,3,4,6-tetra-O-acetyl--D-mannopyranosyl)-1-(1,2,3,4-tetrahydroacridin-9-yl)thiosemicarbazide (2), 2-(1,2,3,4-tetrahydroacridin-9-yl)hydrazono-3-(2,3,4,6-tetra-O-acetyl--D-galactopyranosyl)-1,3-thiazolidin-4-one (3) and [2-(1,2,3,4-tetrahydro-acridin-9-yl)hydrazono-3-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl)-4-oxothiazolidin-5-yliden]acetate (4) were synthesized and their characteristics were investigated. All of the novel derivatives were found to inhibit acetylcholinesterase obtained from Electrophorus electricus at a magnitude of one order less than that of the control tacrine. Derivatives 1-3 were found to be nontoxic towards human neuroblastoma SH-SY5Y cells, while compound 4 was markedly cytotoxic against these cells (IC50 value 2 mu M, 72h). These differences in cytotoxicity were examined further by investigating the uptake and intracellular localization of the tacrine derivatives. Non-cytotoxic derivatives 1-3 were found to localize outside of the nuclei, showing a marked preference for the lysosomes and the mitochondria; in contrast, the cytotoxic derivative 4 was localized in the nuclei of the neuroblastoma cells. Interaction studies revealed that derivative 4 displays a high affinity towards DNA, and also provided evidence of the compound&apos;s ability to inhibit Topo I.

Czech name

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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

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

Medicinal Chemistry Research

ISSN

1054-2523

e-ISSN

—

Volume of the periodical

27

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

2353-2365

UT code for WoS article

000444949700011

EID of the result in the Scopus database

2-s2.0-85053474137