Synthesis and antiproliferative evaluation of novel 8-cyclopentyl-7,8-dihydropteridin-6(5H)-one derivatives as potential anticancer agents.

Bioorganic & Medicinal Chemistry Letters
Qiu LiPei-Liang Zhao

Abstract

Based on our previous work, a novel class of 8-cyclopentyl-7,8-dihydropteridin-6(5H)-one derivatives were synthesized and evaluated as antiproliferative agents. Structure-activity relationship analysis revealed that the greatest activities were achieved with a 4-(4-methylpiperazin-1-yl)aniline group at C-2 position of dihydropteridin-6(5H)-one core, and the most promising compound 6k demonstrated comparable antiproliferative activity with Palbociclib and more potent than our parent derivative 4 toward four cell lines including HCT-116, HeLa, HT-29, and MDA-MB-231 with IC50 values of 3.29, 6.75, 7.56, and 10.30 μM, respectively. Moreover, the mechanism studies revealed that compound 6k could induce cell cycle arrest at G2/M phase via a concentration-dependent manner. In general, these preliminary observations suggested that these compounds could serve as promising scaffolds for further modification to develop novel and highly potent cancer therapy agents.

References

Sep 8, 2010·Bioorganic & Medicinal Chemistry Letters·Kevin K-C LiuAihua Zou
Jun 14, 2012·Journal of the American Chemical Society·Ge-Fei HaoGuang-Fu Yang
Jul 3, 2013·European Journal of Medicinal Chemistry·Antonio GuiradoJesús Gálvez
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May 7, 2016·Chemical & Pharmaceutical Bulletin·Shawkat Ahmed Abdel-MohsenHussein Salama El-Kashef
May 7, 2016·Nucleic Acids Research·Ge-Fei HaoGuang-Fu Yang
Jun 23, 2016·Molecular Cancer Therapeutics·Rosie Elizabeth Ann GutteridgeNihal Ahmad
Apr 15, 2017·European Journal of Medicinal Chemistry·Peng-Cheng DiaoPei-Liang Zhao
Oct 21, 2018·Medicinal Research Reviews·Violeta Carmona-MartínezPilar García-Peñarrubia
Sep 4, 2019·Bioorganic & Medicinal Chemistry Letters·Concepción Sánchez-MartínezAlfonso de Dios
Mar 19, 2020·Cancer Cell·Anne Fassl, Piotr Sicinski
Apr 15, 2020·Cancer Cell·Mónica Álvarez-Fernández, Marcos Malumbres

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