含1,3,4-恶二唑衍生物的二芳基酰胺和二芳基脲的合成及其广谱抗增殖活性
Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole derivatives.
作者信息
Gamal El-Din Mahmoud M, El-Gamal Mohammed I, Abdel-Maksoud Mohammed S, Yoo Kyung Ho, Oh Chang-Hyun
机构信息
Center for Biomaterials, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea; Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki-Giza 12622, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
出版信息
Bioorg Med Chem Lett. 2015 Apr 15;25(8):1692-1699. doi: 10.1016/j.bmcl.2015.03.001. Epub 2015 Mar 7.
A series of diarylamides and diarylureas possessing 1,3,4-oxadiazole scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 58 cell lines of nine different cancer types at the NCI, and compared with Sorafenib as a reference compound. Most of the compounds showed strong and broad-spectrum antiproliferative activities. The diarylurea compound 2g possessing 4-chloro-3-(trifluoromethyl)phenyl terminal moiety showed the highest mean % inhibition value of about 100% over the 58-cell line panel at 10μM concentration. Also compounds 2h, 2l, 2m exhibited mean % inhibition over 90% at 10μM concentration. The IC50 value of compound 2b over SNB-75 CNS cancer cell line was 0.65μM. Compound 2h also exerted submicromolar IC50 values of 0.67, 0.80, and 0.87μM against PC-3 prostate cancer cell line, HCT-116 colon cancer cell line, and ACHN renal cancer cell line, respectively. Compound 2h showed comparable efficacy to Sorafenib.
设计并合成了一系列具有1,3,4-恶二唑骨架的二芳基酰胺和二芳基脲。在NCI对它们针对9种不同癌症类型的58种细胞系进行了体外抗增殖活性测试，并与作为参考化合物的索拉非尼进行了比较。大多数化合物表现出强的和广谱的抗增殖活性。具有4-氯-3-(三氟甲基)苯基末端部分的二芳基脲化合物2g在10μM浓度下在58种细胞系中显示出约100%的最高平均抑制率。化合物2h、2l、2m在10μM浓度下的平均抑制率也超过90%。化合物2b对SNB-75中枢神经系统癌细胞系的IC50值为0.65μM。化合物2h对PC-3前列腺癌细胞系、HCT-116结肠癌细胞系和ACHN肾癌细胞系的IC50值也分别为0.67、0.80和0.87μM，表现出亚微摩尔级的活性。化合物2h显示出与索拉非尼相当的疗效。
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