RT Journal Article
T1 Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays
A1 Salas, Cristian O.
A1 Zarate, Ana Maria
A1 Kryštof, Vladimir
A1 Mella, Jaime
A1 Faundez, Mario
A1 Brea Floriani, José Manuel
A1 Loza García, María Isabel
A1 Brito, Ivan
A1 Hendrychová, Denisa
A1 Jorda, Radek
A1 Cabrera, Alan R.
A1 Tapia, Ricardo A.
A1 Espinosa Bustos, Christian
K1 Cancer
K1 Purine Derivatives
K1 Cytotoxicity
K1 3D-QSAR
K1 Apoptosis
K1 Cell Cycle
AB 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
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/21689
UL http://hdl.handle.net/10347/21689
LA eng
NO O. Salas, C.; Zarate, A.M.; Kryštof, V.; Mella, J.; Faundez, M.; Brea, J.; Loza, M.I.; Brito, I.; Hendrychová, D.; Jorda, R.; Cabrera, A.R.; Tapia, R.A.; Espinosa-Bustos, C. Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays. Int. J. Mol. Sci. 2020, 21, 161.
NO Financial support was received from FONDECYT (Research Grant N◦ 1161816) and FONDEQUIPprogram CONICYT EQM 160042, Czech Science Foundation (19-09086S) and Palacky University(IGA_PrF_2019_013) and Xunta de Galicia (ED431C 2018/21) and European Regional Development Fund (Project ENOCH, N◦ CZ.02.1.01/0.0/0.0/16_019/0000868)
DS Minerva
RD 22 abr 2026