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 ASEP 0523953 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Promising 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 autorů 13 Číslo článku 161 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. slova 3d-qsar ; Apoptosis ; Cancer ; Cell cycle ; Cytotoxicity ; Purine derivatives Vědní obor RIV FD - Onkologie a hematologie Obor OECD Oncology Způsob publikování Open access Institucionální podpora UEB-Q - RVO:61389030 UT WOS 000515378000161 EID SCOPUS 85077996434 DOI 10.3390/ijms21010161 Anotace 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. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2021 Elektronická adresa http://doi.org/10.3390/ijms21010161
Počet záznamů: 1