Ethacrynic acid(EA）是谷胱甘肽转移酶P1-1 (glutathione S-transferase P1-1 ,GST P1-1) 抑制剂，具有弱的抗肿瘤细胞增殖活性。将EA分子中的羧基酯化增加了其抗细胞增殖的能力。利用生物电子等排原理，我们设计合成了一系列新型的含有噁二唑杂环的EA衍生物，测定了化合物对GSTP1-1的抑制活性以及对人急性早幼粒白血病细胞株（HL-60）的生长抑制活性，并对其构效关系进行了研究。我们的实验据显示，该类EA衍生物对肿瘤细胞生长抑制活性提高，其中大部分化合物对GSTP1-1的抑制活性优于EA或与EA相似。化合物6u是对肿瘤细胞生长抑制具有很好活性的化合物之一，但对GSTP1-1基本无抑制活性。化合物6r和6s对多种实体肿瘤细胞系的半数生长抑制浓度均低于5 μM，是有效的肿瘤细胞生长抑制剂。实验结果表明，该类含噁二唑杂环的EA衍生物通过依赖于GSTP1-1和/或不依赖于GSTP1-1的途径发挥抗肿瘤作用，是一类潜在的有开发前景的抗肿瘤药物。

Ethacrynic acid (EA)is a glutathione S-transferase P1-1 (GSTP1-1) inhibitor with weak antiproliferative ability in tumor cells. Esterification of the EA carboxyl group increased the antiproliferative ability. Using the principle of bioisosterism, a series of novel EA analogs containing a heterocycle oxadiazole were designed and synthesized. The structure-activity relationships of inhibiting GST P1-1 activity and cell proliferation of those EA oxadiazole analogs were investigated in human leukemia HL-60 cells. Our data revealed that those EA oxadiazole analogs had improved antiproliferative activity and most of them had similar or better inhibitory effects on GST P1-1 activity than EA. Compound 6u was one of the potent antiproliferative agents without inhibition of GST P1-1 activity. Compound 6r and 6s were potent cell growth inhibitors in several solid tumor cell lines with the concentrations inhibiting half of cell growth less than 5 μM. Our data suggest that these EA oxadiazole analogs are promising antitumor agents which may act through GST P1-1 inhibition-dependent and/or -independent pathways.

Ethacrynic acid(EA）是谷胱甘肽转移酶P1-1 (glutathione S-transferase P1-1 ,GST P1-1) 抑制剂，具有弱的抗肿瘤细胞增殖活性。将EA分子中的羧基酯化增加了其抗细胞增殖的能力。利用生物电子等排原理，我们设计合成了一系列新型的含有噁二唑杂环的EA衍生物，测定了化合物对GSTP1-1的抑制活性以及对人急性早幼粒白血病细胞株（HL-60）的生长抑制活性，并对其构效关系进行了研究。我们的实验据显示，该类EA衍生物对肿瘤细胞生长抑制活性提高，其中大部分化合物对GSTP1-1的抑制活性优于EA或与EA相似。化合物6u是对肿瘤细胞生长抑制具有很好活性的化合物之一，但对GSTP1-1基本无抑制活性。化合物6r和6s对多种实体肿瘤细胞系的半数生长抑制浓度均低于5 μM，是有效的肿瘤细胞生长抑制剂。实验结果表明，该类含噁二唑杂环的EA衍生物通过依赖于GSTP1-1和/或不依赖于GSTP1-1的途径发挥抗肿瘤作用，是一类潜在的有开发前景的抗肿瘤药物。