Počet záznamů: 1  

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

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    SYSNO ASEP0523953
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevPromising 2,6,9-trisubstituted purine derivatives for anticancer compounds: Synthesis, 3D-QSAR, and preliminary biological assays
    Tvůrce(i) Salas, C. O. (CL)
    Zarate, A. M. (CL)
    Kryštof, Vladimír (UEB-Q) RID, ORCID
    Mella, J. (CL)
    Faundez, M. (CL)
    Brea, J. (ES)
    Loza, M. I. (ES)
    Brito, I. (CL)
    Hendrychová, Denisa (UEB-Q) ORCID
    Jorda, Radek (UEB-Q) ORCID, RID
    Cabrera, A. R. (CL)
    Tapia, R. A. (CL)
    Espinosa-Bustos, C. (CL)
    Celkový počet autorů13
    Číslo článku161
    Zdroj.dok.International Journal of Molecular Sciences. - : MDPI
    Roč. 21, č. 1 (2020)
    Poč.str.28 s.
    Jazyk dok.eng - angličtina
    Země vyd.CH - Švýcarsko
    Klíč. slova3d-qsar ; Apoptosis ; Cancer ; Cell cycle ; Cytotoxicity ; Purine derivatives
    Vědní obor RIVFD - Onkologie a hematologie
    Obor OECDOncology
    Způsob publikováníOpen access
    Institucionální podporaUEB-Q - RVO:61389030
    UT WOS000515378000161
    EID SCOPUS85077996434
    AnotaceWe 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.
    PracovištěÚstav experimentální botaniky
    KontaktDavid Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469
    Rok sběru2021
    Elektronická adresahttp://doi.org/10.3390/ijms21010161
Počet záznamů: 1