Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines
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Temburnikar, Kartik W., Christina R. Ross, Gerald M. Wilson, Jan Balzarini, Brian M. Cawrse, and Katherine L. Seley-Radtke. “Antiproliferative Activities of Halogenated Pyrrolo[3,2-d]Pyrimidines.” Bioorganic & Medicinal Chemistry 23, no. 15 (August 1, 2015): 4354–63. https://doi.org/10.1016/j.bmc.2015.06.025.
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Abstract
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.