Preparation and cytotoxicity toward cancer cells of mono(arylinaino) derivatives of β-lapachone
Preparation and cytotoxicity toward cancer cells of mono(arylinaino) derivatives of β-lapachone
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DOI：
10.1021/jm010050u
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发表时间：
2001-07-19
影响因子：
7.3
通讯作者：
Burton, G
中科院分区：
文献类型：
--
作者：
Di Chenna, PH;Benedetti-Doctorovich, V;Burton, G
在过量的三乙胺/四氯化钛(4：1)存在下，由β-罗巴酮(1)衍生的单芳亚胺邻苯二酮与少量芳胺反应，得到了一种区域和立体专一性的单芳亚胺邻苯二酮的合成方法。单晶X-射线分析表明，亚胺只在6位生成，给出Z非对映异构体。对55个人癌细胞的体外细胞毒性试验表明，对-硝基苯亚胺(5)的活性显著降低，而苯亚胺(2)、对甲基苯亚胺(3)和对甲氧基苯亚胺(4)保留(或更好)了亲代苯醌的大部分细胞毒性和选择性。中空纤维对12个人类肿瘤细胞株的体内初步测试表明，尽管β-雷帕酮失败，但化合物2和3在净细胞杀伤率方面得分很好。
A regio- and stereospecific synthesis of monoarylimino o-quinones derived from beta -lapachone (1) was achieved by treatment of the quinone with a slight excess of an arylamine in the presence of an excess of triethylamine/titanium tetrachloride 4:1. Imine formation occurred exclusively at position 6, giving the Z diastereomer, as determined by single-crystal X-ray analysis. In vitro tests for cytotoxicity in 55 human cancer cell cultures showed a substantial loss in activity for the p-nitrophenylimine (5), whereas the phenylimine (2), p-methylphenylimine (3), and p-methoxyphenylimine (4) retained (or bettered) most of the cytotoxicity and selectivity of the parent quinone. Preliminary in vivo testing in hollow fiber assays against a standard panel of 12 human tumor cell lines showed that although beta -lapachone failed, compounds 2 and 3 had good scores with net cell kills.