Abstract
Halogenated thieno[3,2-d]pyrimidines exhibit antiproliferative activity against a variety of cancer cell models, such as the mouse lymphocytic leukemia cell line L1210 in which they induce apoptosis independent of cell cycle arrest. Here we assessed these activities on MDA-MB-231 cells, a well-established model of aggressive, metastatic breast cancer. While 2,4-dichloro[3,2-d]pyrimidine was less toxic to MDA-MB-231 cells than previously observed in the L1210 model, flow cytometry analysis showed that MDA-MB-231 cell death involved arrest at the G2/M stage of the cell cycle. Conversely, the introduction of bromine at C7 of the 2,4-dichloro[3,2-d]pyrimidine eliminated cell type-dependent differences in cytotoxicity or cell cycle status. Together, these data indicate that a substituent at C7 can profoundly modify the cytotoxic mechanism of halogenated thieno[3,2-d]pyrimidines in a cell type-specific manner.
References
Jul 10, 1999·International Journal of Cancer. Journal International Du Cancer·W Nieves-Neira, Y Pommier
Nov 10, 2000·Breast Cancer Research and Treatment·D A Gewirtz
Oct 18, 2005·Molecular Cancer Therapeutics·David L MorseRobert J Gillies
Dec 13, 2006·Cancer Cell·Richard M NeveJoe W Gray
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
May 28, 2009·Cancer Research·Jing LuDihua Yu
Mar 11, 2010·Current Pharmaceutical Design·José PortugalMarc Bataller
May 22, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·David Eriksson, Torgny Stigbrand
Jan 25, 2011·Nature Reviews. Cancer·Giulio FranciaRobert S Kerbel
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jul 23, 2011·Breast Disease·Kathryn J ChavezStanley Lipkowitz
Sep 3, 2011·Breast Cancer Research : BCR·Deborah L Holliday, Valerie Speirs
Oct 11, 2011·Journal of Medicinal Chemistry·Daniel P SutherlinAlan Olivero
Oct 15, 2011·Molecular Cancer Therapeutics·Jeffrey J WallinLori S Friedman
Feb 18, 2012·Journal of Medicinal Chemistry·Simon MathieuJoachim Rudolph
May 26, 2012·Journal of Medicinal Chemistry·Brian S SafinaDaniel P Sutherlin
Oct 19, 2012·Cell Death & Disease·K-S ChanH-Y Li
Sep 10, 2013·Nature Chemical Biology·Mohammad Fallahi-SichaniPeter K Sorger
Mar 19, 2014·Bioorganic & Medicinal Chemistry·Kartik W TemburnikarKatherine L Seley-Radtke
Citations
May 13, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qiumeng ZhangWei Lu
Jan 12, 2017·ChemMedChem·Rosemary BassDaniele Castagnolo
Feb 8, 2018·PloS One·Thais Russo-AbrahãoJosé Roberto Meyer-Fernandes
Jan 18, 2018·Acta Pharmaceutica : a Quarterly Journal of Croatian Pharmaceutical Society and Slovenian Pharmaceutical Society, Dealing with All Branches of Pharmacy and Allied Sciences·Hend N Hafez, Abdel-Rhman B A El-Gazzar
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ameen Ali Abu-HashemMagdi E A Zaki