Cytotoxic 1,3-diarylidene-2-tetralones and related compounds
Cytotoxic 1,3-diarylidene-2-tetralones and related compounds
复制标题
DOI：
10.1016/s0223-5234(02)01402-2
复制
发表时间：
2002-10-01
影响因子：
6.7
通讯作者：
Stables, JP
中科院分区：
文献类型：
--
作者：
Dimmock, JR;Padmanilyam, MP;Stables, JP
合成了许多1，3-亚芳基-2-四氢萘酮1、2和4，并证明了对鼠P388和L12 - 10细胞以及人Molt 4/C8和CEM T-淋巴细胞的细胞毒性活性。通常，相关的1-亚芳基-2-四氢萘酮3在这些筛选中具有比系列1和4中的化合物更低的效力。大约一半的化合物针对一组人类肿瘤细胞系进行了评价。在该筛选中，大多数烯酮比已建立的抗癌剂美法仑更具细胞毒性，并且一些对白血病和结肠癌细胞表现出选择性毒性。代表性化合物的作用模式包括干扰核酸和蛋白质的生物合成以及改变氧化还原电位。当腹膜内给予小鼠时，化合物耐受性良好。因此，这些新的烯酮是有前途的原型分子，由于其有效的细胞毒性特性和缺乏显着的小鼠毒性。(C)2002年由Editions scientifiques et medicales Elsevier SAS出版
A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L 12 10 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity. (C) 2002 Published by Editions scientifiques et medicales Elsevier SAS.