Synthesis and antiproliferative evaluation of novel 8-cyclopentyl-7,8-dihydropteridin-6(5H)-one derivatives as potential anticancer agents
| Autor: | Pei-Liang Zhao, Ren-Xin He, Yu-Feng Ma, Wen-Wei You, Qiu Li, Xian-Sen Huo, Lin Chen, Xie-Er Jian, Yu Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Cell cycle checkpoint
Clinical Biochemistry Cancer therapy Pharmaceutical Science Antineoplastic Agents Palbociclib 01 natural sciences Biochemistry HeLa chemistry.chemical_compound Structure-Activity Relationship Aniline Derivative (finance) Cell Line Tumor Drug Discovery Humans Molecular Biology Cell Proliferation biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Pteridines Organic Chemistry biology.organism_classification Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Cell culture Antiproliferative Agents Molecular Medicine Drug Screening Assays Antitumor |
| Zdroj: | Bioorganicmedicinal chemistry letters. 31 |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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