2-溴-4’-羟基查尔酮-苯磺酸酯衍生物的合成及抗肿瘤活性

Synthesis and antitumor activity of 2-bromo-4'-hydroxyl chalcone benzene sulfonate derivatives

摘要:

基于药效团拼合原理设计并合成23个未见文献报道的 (E)-4-[3-(2-溴苯基)丙烯酰基]苯基-取代苯磺酸酯衍生物（产率：60.9-80.3%），通过1HNMR、MS、13CNMR确证了产物结构，采用MTT法以5-氟尿嘧啶和伊马替尼为阳性对照药，以人宫颈癌Hela细胞、人肺癌A549细胞和人慢性粒细胞白血病K562细胞为测试细胞株评价了目标化合物的体外抗肿瘤活性。目标化合物Ⅴp表现出最强的A549细胞增殖抑制活性(半抑制浓度IC50 = 7.53 μmol/L)，优于阳性对照药5-氟尿嘧啶(IC50 = 8.1 μmol/L)，目标化合物Ⅴt表现出最强的K562细胞增殖抑制活性(IC50 = 4.47 μmol/L)，目标化合物Ⅴd表现出最强的Hela细胞增殖抑制活性（IC50 = 4.53 μmol/L），比阳性对照药5-氟尿嘧啶(IC50 = 13.5 μmol/L)强约3倍。目标化合物Ⅴd对A549细胞（IC50 = 8.0 μmol/L）和K562细胞（IC50 = 7.81 μmol/L）也表现出强的增殖抑制活性，值得进一步深入研究。

Abstract:

Twenty-three (E)-4-(3-(2-bromophenyl) acryyl) phenyl - substituted benzenesulfonic ester derivatives were designed and synthesized based on the pharmacophore combination principle (yield: 60.9 to 80.3%), and their structures were confirmed by 1H NMR, MS and 13C NMR. The in vitro antitumor activity of the target compound was evaluated by MTT assay using 5-fluorouracil and imatinib as positive control, human cervical cancer Hela cells, human lung cancer A549 cells and human chronic myelocytic leukemia K562 cells as test cell lines. Target compound Vp exhibited the strongest A549 cell proliferation inhibitory activity (IC50 = 7.53 μmol/L), better than the positive control drug 5-fluorouracil (IC50 = 8.1 μmol/L), target compound Vt exhibited the strongest inhibitory activity of K562 cell proliferation inhibition (IC50 = 4.47 μmol/L), target compound Vd exhibited the strongest Hela cell proliferation inhibitory activity (IC50 = 4.53 μmol/L), than positive control drug 5-fluorouracil (IC50 = 13.5 μmol/L) is approximately 3 times stronger, and the target compound Vd also exhibits strong proliferation inhibitory activity against A549 cells (IC50 = 8.0 μmol/L) and K562 cells (IC50 = 7.81 μmol/L), which deserves further study.