Promising 2,6,9-trisubstituted purine derivatives for anticancer compounds: Synthesis, 3D-QSAR, and preliminary biological assays

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F20%3A00523953" target="_blank" >RIV/61389030:_____/20:00523953 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/20:73604843

Result on the web

<a href="http://doi.org/10.3390/ijms21010161" target="_blank" >http://doi.org/10.3390/ijms21010161</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21010161" target="_blank" >10.3390/ijms21010161</a>

Result language

angličtina

Original language name

Promising 2,6,9-trisubstituted purine derivatives for anticancer compounds: Synthesis, 3D-QSAR, and preliminary biological assays

Original language description

We designed, synthesized, and evaluated novel 2,6,9-trisubstituted purine derivatives for their prospective role as antitumor compounds. Using simple and efficient methodologies, 31 compounds were obtained. We tested these compounds in vitro to draw conclusions about their cell toxicity on seven cancer cells lines and one non-neoplastic cell line. Structural requirements for antitumor activity on two different cancer cell lines were analyzed with SAR and 3D-QSAR. The 3D-QSAR models showed that steric properties could better explain the cytotoxicity of compounds than electronic properties (70% and 30% of contribution, respectively). From this analysis, we concluded that an arylpiperazinyl system connected at position 6 of the purine ring is beneficial for cytotoxic activity, while the use of bulky systems at position C-2 of the purine is not favorable. Compound 7h was found to be an effective potential agent when compared with a currently marketed drug, cisplatin, in four out of the seven cancer cell lines tested. Compound 7h showed the highest potency, unprecedented selectivity, and complied with all the Lipinski rules. Finally, it was demonstrated that 7h induced apoptosis and caused cell cycle arrest at the S-phase on HL-60 cells. Our study suggests that substitution in the purine core by arylpiperidine moiety is essential to obtain derivatives with potential anticancer activity.

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

30204 - Oncology

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

2020

Confidentiality

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

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

1

Country of publishing house

CH - SWITZERLAND

Number of pages

28

Pages from-to

161

UT code for WoS article

000515378000161

EID of the result in the Scopus database

2-s2.0-85077996434