新型四氢-2H-吡喃并[3,2-c]哒嗪-3(6H)-酮衍生物的设计与合成及其作为潜在抗癌剂的研究。
Design and synthesis of novel tetrahydro-2H-Pyrano[3,2-c]pyridazin-3(6H)-one derivatives as potential anticancer agents.
机构信息
College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah, P. O. Box 27272, Sharjah, United Arab Emirates.
出版信息
Eur J Med Chem. 2010 Dec;45(12):5724-31. doi: 10.1016/j.ejmech.2010.09.029. Epub 2010 Sep 17.
Polyfunctional tetrahydro-2H-pyrano[3,2-c]pyridazin-3(6H)-one derivatives were synthesized and biologically evaluated as novel anticancer agents. These motifs were produced by a five-step reaction sequence in which the Achmatowicz oxidative cyclization, is the basic core for such synthesis. Compounds 15f, 16c, and 16d showed antiproliferative activity against the SK-BR-3 breast cancer cell line. Importantly, 16c and 16d showed the highest efficacy, being approximately 30-fold more potent against SK-BR-3 (IC50 0.21 and 0.15 μM, respectively) compared to other cancer cell lines tested. In addition, 16c and 16d displayed about 295 fold less toxicity against normal breast cell line MCF10A compared to SK-BR-3 breast cancer cells. These compounds form the foundation for further investigation in our continuing efforts to develop potent anticancer agents.
合成了多官能四氢-2H-吡喃并[3,2-c]哒嗪-3(6H)-酮衍生物，并将其作为新型抗癌剂进行了生物学评价。这些基序通过五步反应序列合成，其中 Achmatowicz 氧化环化是这种合成的基本核心。化合物 15f、16c 和 16d 对 SK-BR-3 乳腺癌细胞系表现出抗增殖活性。重要的是，与其他测试的癌细胞系相比，16c 和 16d 对 SK-BR-3 的功效最高，约为 30 倍（IC50 分别为 0.21 和 0.15 μM）。此外，与 SK-BR-3 乳腺癌细胞相比，化合物 16c 和 16d 对正常乳腺细胞系 MCF10A 的毒性约低 295 倍。这些化合物为我们继续开发有效的抗癌剂的努力奠定了基础。
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