新型哌啶二酮类似物作为乳腺癌细胞生长抑制剂

Novel piperidinedione analogs as inhibitors of breast cancer cell growth.

作者信息

Abou-Zeid L A, el-Mowafy A M, el-Ashmawy M B, Hendry L B, Abdelal A M, Badria F A

机构信息

Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

出版信息

Arch Pharm (Weinheim). 2000 Dec;333(12):431-4. doi: 10.1002/1521-4184(200012)333:12<431::aid-ardp431>3.0.co;2-m.

DOI:10.1002/1521-4184(200012)333:12<431::aid-ardp431>3.0.co;2-m

PMID:11199474

Abstract

We previously reported the utility of antineoplaston-A10 (3-phenylacetylamino-2,6-piperidinedione) as an endogenous cancer protector and immune modulator in breast cancer patients (Cancer Lett., 2000, 157, 57). In this study, four new piperidinedione A10 analogs were synthesized and tested for their antimitotic activity on a human breast cancer cell line against the prototype A10 and the antibreast cancer drug tamoxifen. Moreover, the DNA binding capacity of such compounds was evaluated against A10, (E)-3-(4-Nitrocinnamoylamino)-2,6-piperidinedione "3B" and (E)-3-(4-hydroxycinnamoylamino)-2,6-piperidinedione "3D" were several-fold more potent antiproliferative agents than A10 and tamoxifen. They also had significantly higher capacity to bind DNA than A10. Conversely, (E)-3-(cinnamoylamino)-2,6-piperidinedione "3A" and (E)-3-(4-methoxycinnamoylamino)-2,6-piperidinedione) "3C" had weaker biological profiles than the lead compound A10. Detailed synthetic, spectroscopic, and biological data are reported.

摘要

我们之前报道了抗肿瘤素-A10（3-苯乙酰氨基-2,6-哌啶二酮）作为乳腺癌患者内源性癌症保护剂和免疫调节剂的效用（《癌症通讯》，2000年，第157卷，第57页）。在本研究中，合成了四种新的哌啶二酮A10类似物，并测试了它们对人乳腺癌细胞系的抗有丝分裂活性，与原型A10和抗乳腺癌药物他莫昔芬进行比较。此外，评估了这些化合物与A10的DNA结合能力，(E)-3-(4-硝基肉桂酰氨基)-2,6-哌啶二酮“3B”和(E)-3-(4-羟基肉桂酰氨基)-2,6-哌啶二酮“3D”是比A10和他莫昔芬效力高几倍的抗增殖剂。它们与DNA结合的能力也明显高于A10。相反，(E)-3-(肉桂酰氨基)-2,6-哌啶二酮“3A”和(E)-3-(4-甲氧基肉桂酰氨基)-2,6-哌啶二酮“3C”的生物学特性比先导化合物A10弱。报告了详细的合成、光谱和生物学数据。