基于4H-色烯的抗多药耐药HL60/MX2人白血病抗癌剂：第4位和第6位的构效关系
4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.
作者信息
Puppala Manohar, Zhao Xinghua, Casemore Denise, Zhou Bo, Aridoss Gopalakrishnan, Narayanapillai Sreekanth, Xing Chengguo
机构信息
Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA; College of Traditional Chinese Veterinary Medicine, Agricultural University of Hebei, Baoding, Hebei 071001, People's Republic of China.
出版信息
Bioorg Med Chem. 2016 Mar 15;24(6):1292-7. doi: 10.1016/j.bmc.2016.01.056. Epub 2016 Feb 1.
Abstract
4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization.
摘要
例如，基于4H-色烯的化合物CXL017、CXL035和CXL055具有独特的抗癌潜力，它们能选择性地杀死多药耐药癌细胞。本文报道了扩展的构效关系（SAR）研究，重点关注第4位的酯官能团和第6位的构象。在这两个位置上，关于细胞毒性效力以及亲代HL60细胞和多药耐药HL60/MX2细胞之间的选择性，都观察到了明显的构效关系。这些结果为未来的药物优化提供了关键指导。
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