首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Synthesis of novel aminoquinonoid analogues of diospyrin and evaluation of their inhibitory activity against murine and human cancer cells.
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Synthesis of novel aminoquinonoid analogues of diospyrin and evaluation of their inhibitory activity against murine and human cancer cells.

机译:薯py苷新型氨基喹诺酮类似物的合成及其对鼠和人癌细胞的抑制活性评估。

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摘要

The synthesis and tumor-inhibitory activity of a series of aminonaphthoquinone derivatives of diospyrin, which was isolated from Diospyros montana Roxb., are presented here for the first time. An aminoacetate derivative showed the maximum (approximately 93%) increase in life span in vivo against murine Ehrlich ascites carcinoma (EAC) at a dose of 1 mg kg(-1)day(-1) (ip; five doses), and the lowest IC50 (0.06 microM) in vitro. Further, the same analogue also exhibited considerable enhancement in antiproliferative activity when evaluated against human cell lines, viz. malignant skin melanoma and epidermoid laryngeal carcinoma (IC50=0.06 and 0.92 microM, respectively) in comparison to the natural precursor, diospyrin (IC50=0.82 and 3.58 microM, respectively). Moreover, diospyrin and all its derivatives were found to show significantly greater (approximately 17- to 1441-fold) cytotoxicity against the tumor cells as compared to normal human lymphocytes. All these quinonoids generated substantial amounts of reactive oxygen species in EAC cells, more or less commensurate to their respective IC50 values.
机译:首次从Diospyros montana Roxb。中分离出的一系列Diospyrin氨基萘醌衍生物的合成和抑瘤活性。氨基乙酸衍生物在1 mg kg(-1)day(-1)(ip; 5剂)剂量下对鼠艾氏腹水癌(EAC)的体内寿命最大(约93%)增加,并且体外最低IC50(0.06 microM)。此外,当针对人类细胞系进行评估时,相同的类似物还表现出相当大的抗增殖活性。恶性皮肤黑素瘤和表皮样喉癌(分别为IC50 = 0.06和0.92 microM)与天然前驱体薯os素(分别为IC50 = 0.82和3.58 microM)相比。而且,发现薯os苷及其所有衍生物对肿瘤细胞显示出比正常人淋巴细胞明显更大的细胞毒性(约17至1441倍)。所有这些醌类化合物在EAC细胞中产生了大量的活性氧,或多或少与其各自的IC50值相当。

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