新型吲唑-查尔酮杂合物的合成及抗肿瘤活性

设计并合成了一系列新型含查尔酮-吲唑杂合衍生物,并对其体外肿瘤活性进行初步研究。 先以2,6-二氟苯腈和吗啉为起始原料,经过取代和环合两步反应合成4-吗啉-3-氨基-1H-吲唑。 4-吗啉-3-氨基-1H-吲唑与含羧基的查尔酮中间体与经过酰胺化反应制备了9个新型含查尔酮-吲唑杂合衍生物,其结构经傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(NMR)、质谱(MS)和元素分析确证。 采用MTT法,以索拉菲尼为阳性对照药,以人胃癌细胞株(MKN45)和人肺癌细胞株(A549)为测试细胞株对目标化合物进行抗肿瘤活性评价。 结果表明,大部分目标化合物显示了较好的抗肿瘤活性,其中化合物4a和4d活性较好,其抑制人胃癌细胞株MKN45的IC₅₀分别为2.65和3.55 μmol/L,均优于阳性对照药索拉菲尼(IC₅₀=4.69 μmol/L)。

Synthesis and Antiproliferative Activity of Novel Indazole-Chalcone Hybrids

Nine novel indazole-chalcone hybrids(4a-4i) have been synthesized by condensation of substituted 4-(3-oxo-3-phenylprop-1-en-1-yl) benzoic acid with 4-morpholino-1H-indazol-3-amine prepared from 2,6-difluorobenzonitrile by amination with morpholine and then cyclisation with hydrazine hydrate. Their chemical structures were confirmed by Fourier transform infrared spectrometer(FTIR), nuclear magnetic resonance spectroscopy(NMR), mass spectrometry(MS) and elemental analysis. Compounds(4a-4i) were screened for in vitro antiproliferative activities against human gastric cancer cell line(MKN45) and human lung adenocarcinoma cell line(A549). Most of the designed compounds were found to exhibit potential antiproliferative activities. Among them, compounds 4a and 4d exhibited remarkable inhibitory activity against MKN45 cell lines with IC₅₀ value of 2.65 and 3.55 μmol/L, respectively, which were more potent than that of the positive control sorafenib(IC₅₀=4.69 μmol/L).