Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines

作者：Temburnikar Kartik W; Ross Christina R; Wilson Gerald M; Balzarini Jan; Cawrse Brian M; Seley Radtke Katherine L^*

来源：Bioorganic & Medicinal Chemistry, 2015, 23(15): 4354-4363.

DOI：10.1016/j.bmc.2015.06.025

• Thieno[3,2-d]pyrimidine
• Heterocyclic chemistry
• Cytostatic
• Apoptosis
• Cell cycle arrest

In vitro evaluation of the halogenated pyrrolo[3,2-d]pyrimidines identified antiproliferative activities in compounds 1 and 2 against four different cancer cell lines. Upon screening of a series of pyrrolo[3, 2-d] pyrimidines, the 2,4-Cl compound 1 was found to exhibit antiproliferative activity at low micromolar concentrations. Introduction of iodine at C7 resulted in significant enhancement of potency by reducing the IC50 into sub-micromolar levels, thereby suggesting the importance of a halogen at C7. This finding was further supported by an increased antiproliferative effect for 4 as compared to 3. Cell-cycle and apoptosis studies conducted on the two potent compounds 1 and 2 showed differences in their cytotoxic mechanisms in triple negative breast cancer MDA-MB-231 cells, wherein compound 1 induced cells to accumulate at the G2/M stage with little evidence of apoptotic death. In contrast, compound 2 robustly induced apoptosis with concomitant G2/M cell cycle arrest in this cell model.

• 出版日期2015-8-1
• 单位河北医科大学