【作者】 郭春丽；

【导师】 杨频；

【作者基本信息】 山西大学 ， 无机化学， 2004， 硕士

【摘要】 低氧是人和动物肿瘤的共同特征，绝大多数人的氧分压低于肿瘤起源的正常细胞，它是肿瘤发展过程所必须经历的环境条件之一。它的存在对肿瘤的发展、恶性侵袭、运处转移，乃至肿瘤对放疗、化疗的抵抗等方面都起着重要的作用。临床和动物模型都已证实实体瘤内确实存在低氧细胞。目前为克服肿瘤低氧细胞对治疗的抗拒性，采取了许多不同的方法，包括加增敏剂、用生物还原剂、微波治疗等。 尽管人们采取了许多克服肿瘤低氧的措施，企图提高肿瘤治疗疗效，但临床结果均不令人满意。多年来肿瘤治疗学家和研究人员一直致力于寻找有效的低氧细胞毒性药及有效的杀灭手段。九十年代，新西兰大学Ware教授另辟途径，利用低氧肿瘤细胞易于引发生物还原性反应的条件，提出一种新型的解决方法—低氧选择性抗癌药物(Hypoxic selective agents)。此方法的设计原理为：前体药物在肿瘤低氧区经过生物还原反应后释放出扩散性细胞毒剂，细胞毒剂比前体化合物有更高的毒性且足够稳定，并且可以从低氧区扩散到有氧区，这样可以达到对实体瘤主要区域的有效杀伤。 利用以上原理．我们选择钴原子作为中心原子，选择氮芥为活性配体。本文中，我们以研究三价钴配合物的配位化学、结构特性及寻找更好的抗癌活性为目的，查阅大量文献后，主要作了以下几个方面的工作： 1．本文中我们总结了三价钴配合物的研究现状，合成出3-甲基2，4-戊二酮、3-乙基2，4-戊二酮、3-烯丙基2，4-戊二酮、3，4-二乙酰基2，5-己二酮四个辅助配体，和双-二氯乙基胺盐酸盐、双-三氯乙基胺盐酸盐、双-二溴乙基胺氢溴酸盐、二-β-氯乙基草酰胺四个活性配体。 2．通过无机合成，合成了九个三价钴配合物，其中六个是文献中没有报道的。他们都以乙酰丙酮类化合物作为辅助配体，以氮芥类化合物作为活性配体的络合物。 3．应用红外光谱、元素分析、x-衍射等手段对合成的配体及配合物的结构进行了表山西大学2004届硕士研究生毕业论文 征。4.把合成的络合物用电泳技术进行了活性评估，得出co(acac):N压BBA比其它二价 钻配合物有较高的切害U活性更多还原

【Abstract】 Hypoxic phenomenon is a common character in tumor cells of human beings and animals. And oxygen pressure in most of people is lower than natural tissue of tumor origin. Hypoxia is one of environmental conditions which tumor development must go through. Its being is important on some sides, such as tumor development, malignant attack, distant transfer, and tumor resisting to radioactive therapy and chemical therapy. There are some evidences .in clinic and animal models that ensure hypoxic cell’s existing in solid tumor. People take different measures to control the resisting to hypoxic cell in the therapy up to now, including adding radiosensitizer, using bioreductive agents, microwave therapy and so on.People take many steps to improve the tumor curative effect, but the results are not contented. Tumor therapist and researcher are applying themselves to look for a effective hypoxic toxic medicine or effective kill measures. In the 1990’ s, professor Ware in New Zealand university find other ways and put forward new resolvent梙ypoxic-selective agents. The design principle is as following: Hypoxia-selective prodrugs can release diffusible cytotoxins on bioreduction in hypoxic regions. Such diffusible cytotoxins are required to be much more cytotoxic than the parent prodrug, to be sufffciently stable to allow them to diffuse from the hypoxic regions, and to be adequately, effective against all major tumor cell subpopulations.This paper selects cobalt as center atom and nitrogen mustard as bioactive ligands. In this paper, in order to study the structure characteristic of cobalt(III) complexes and find the new antitumor bioactivity, the work mention below were carried out:1.We have synthesized four secondary Ligands: Meacac, Etacac, Alacac, TAT, and four bioactive ligands: BCA.HCl, BBA.HBr, TCA.HC1, BCOA.2.We have synthesized nine complexes, six of which are not reported, such as Co (acac),NO1BBA, Co(Meacac).NO2BBA. .3.Their element analysis, infrared spectra and nuclear magnetic resonance hydrogen spectra were measured and structures of the ligands and complexes were determinded.4.We have evaluated the bioactivity of three complexes for the cleavage of PBR322 DNA. We can know Co(acac).NO2BBA is better than other complexes in the cleavage of DNA.更多还原