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系统比较研究芳香异羟肟酸二丁基锡抗癌先导化合物二-(苯甲酰异羟肟酸)二正丁基合锡(DBDBT)配体苯环上引入不同电负性取代基团得到的化合物二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)和二-(4-甲氧基-苯甲酰异羟肟酸)二正丁基合锡(DBDMT)在大鼠体内的组织分布规律及其差异,探讨结构-组织分布-抗癌活性间的关系.静注3min后,DBDCT可迅速分布到各组织,主要分布在肾上腺,其次是十二指肠和肾,给药10min后肝脏、肠、胃壁、肺、肌肉和脂肪等组织浓度较高;而DBDMT只能分布于脑、心脏、肾、脾等少数几种组织.前期研究中DBDCT对人肝癌Bel-7402、人胃腺癌SGC-7901、卵巢癌Hela等细胞株具有比DBDMT更强的抗癌活性可能与DBDCT在肝脏、胃壁和卵巢中有较高分布、但这三个组织中几乎检测不到DBDMT有关.可见先导化合物DBDBT的配体苯环上引入的取代基团的电负性可明显影响其相应衍生物在大鼠体内的组织分布,从而可能导致对不同组织肿瘤的抗癌活性的较大差别,该研究为先导化合物DBDBT的进一步结构优化提供参考依据.
A systematic comparative study of compounds derived from the introduction of different electron-negative substituent groups on the phenyl ring of the dibutyltin aromatic dihydroxamic acid dibenzotin lead compound di-(benzoylhydroxamic acid) di-n-butyltin (DBDBT) ligand Di-(4-chlorobenzoylhydroxamic acid) di-n-butyltin (DBDCT) and di-(4-methoxy-benzoylhydroxamic acid) di-n-butyltin (DBDMT) The distribution of tissue in rats and its differences, to explore the relationship between structure - tissue distribution - anticancer activity. After intravenous injection of 3min, DBDCT can be quickly distributed to various tissues, mainly in the adrenal gland, followed by the duodenum and In kidney, the concentration of liver, intestine, stomach wall, lung, muscle, fat and other tissues was higher after 10 minutes of administration; DBDMT can only be distributed in a few tissues such as brain, heart, kidney, and spleen. In the previous study, DBDCT was applied to human liver cancer Bel -7402, human gastric adenocarcinoma SGC-7901, ovarian cancer Hela and other cell lines have stronger anti-cancer activity than DBDMT and DBDCT have higher distribution in liver, stomach wall and ovary, but almost no detectable in these three tissues. For DBDMT, the electronegativity of the substituent group introduced on the benzene ring of the ligand DBDBT can obviously affect its phase. Rats derivatives tissue distribution, which may lead to large differences in anticancer activity of different tumor tissue, the study is to further optimize the structure of lead compounds DBDBT provide reference.