细胞毒性
细胞毒性T细胞
立体化学
化学
效力
体外
烷基化
细胞凋亡
细胞培养
生物化学
生物
遗传学
催化作用
作者
Sasmita Das,Umashankar Das,Armando Varela-Ramı́rez,Carolina Lema,Renato J. Aguilera,Jan Balzarini,Erik De Clercq,Stephen G. Dimmock,D. K. J. Gorecki,Jonathan R. Dimmock
出处
期刊:ChemMedChem
[Wiley]
日期:2011-08-08
卷期号:6 (10): 1892-1899
被引量:21
标识
DOI:10.1002/cmdc.201100199
摘要
Abstract The principal objective of this study was the examination of the theory of cytotoxic synergism. In this exploratory study, we tested the hypothesis that doubling the number of sites available for thiol alkylation in a series of candidate cytotoxins increases potency more than two‐fold. This concept was verified in one‐third of our comparisons using human Molt 4/C8 and CEM T‐lymphocytes and murine L1210 cells. In addition, the significant potencies of various members of our compound series justified further studies. Molecular modeling revealed that relative locations of the amidic groups correlate with cytotoxicity. A potent cytotoxic compound, 1,2‐bis(3,5‐dibenzylidene‐4‐oxo‐piperidin‐1‐yl)ethane‐1,2‐dione ( 1 a ) inhibited the growth of a large number of human tumor cell lines and displayed greater toxicity toward certain non‐adherent cells than toward adherent neoplasms or fibroblasts. The mode of action of 1 a includes induction of apoptosis and necrosis.
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