缩氨基硫脲修饰的Strandberg型多钼氧簇有机-无机复合物的设计和生物活性评价

Polyoxometalates(abbreviated as POMs) have gained considerable attentions due to their diverse chemical and structural properties and broad range of pharmacological activities. Many efforts have been made to modify POMs through altering their structure, polarity, charge and composition in order to obtain compounds with superior biological activity , higher physiological stability and lower toxicity. One of the best ways is to introduce organic biological molecules into POMs which were reported to effectively overcome the shortcomings of drug molecules, and show significant synergistic effects. Thiosemicarbazones also possess remarkable anticancer, antibacterial and antiviral activity. However, comparatively few structural and biological studies of polyoxometalates containing thiosemicarbazones are published. In the continuation and extension of our research in the bioactivities of thiosemicarbazones, herein, a series of orgainc–inorganic Strandberg-type polyoxomolybdate clusters [(RPO3)2Mo5O15]6−(R= O, O2CCH2, O2CC2H4) appended with thiosemicarbazones are designed and characterized by elemental analysis, IR, UV, MS, NMR and single-crystal X-ray diffraction studies. Evaluation of in vitro and/or in vivo biological activities as well as mechanism of action are carried out. Our objective is to explore preliminary structure-activity relationships and obtain antitumor candidates of high efficiency and low toxicity. Results of this work provide supporting of experimental data and theoretical guidance for the development and the application of both polyoxometalates and thiosemicarbazones in medicine.

多金属氧簇(多酸, POMs)因其多样的结构特点和药物活性而引起人们的广泛关注。改变多酸的结构、极性、电荷和组成，有望得到活性高、稳定性好、毒性低的多酸化合物。多酸经过有机分子修饰，通过二者的协同作用，增强多酸的生物活性，克服其在应用上的缺陷。缩氨基硫脲衍生物也有着良好的抗癌、抗菌和抗病毒活性。作为我们缩氨基硫脲衍生物研究工作的延续和拓展，本项目设计合成一系列缩氨基硫脲修饰的Strandberg型[(RPO3)2Mo5O15]6−(R= O, O2CCH2, O2CC2H4)多钼氧簇有机-无机复合物，并用元素分析、红外、紫外、质谱、核磁、X-射线单晶衍射等对其进行结构表征。在此基础上，对所制备的复合物进行体外细胞毒性筛选、体内抗肿瘤实验以及抗癌机理研究，初步分析构效关系，寻找高效、低毒的抗肿瘤候选药物。该项目的实施将对缩氨基硫脲及多金属氧簇在药物方面的发展和应用提供实验数据支撑和理论指导。

多金属氧簇(多酸, POMs)因其多样的结构特点和药物活性而引起人们的广泛关注。改变多酸的结构、极性、电荷和组成，有望得到活性高、稳定性好、毒性低的多酸化合物。多酸经过有机分子修饰，通过二者的协同作用，增强多酸的生物活性，克服其在应用上的缺陷。缩氨基硫脲衍生物也有着良好的抗癌、抗菌和抗病毒活性。作为我们缩氨基硫脲衍生物研究工作的延续和拓展，本项目设计合成一系列缩氨基硫脲修饰的Strandberg型多钼氧簇有机-无机复合物，并用元素分析、红外、紫外、质谱、核磁、X-射线单晶衍射等对其进行结构表征。在此基础上，对所制备的化合物进行体外细胞毒性筛选、体内抗肿瘤实验以及抗癌机理研究，初步分析构效关系，寻找高效、低毒的抗肿瘤候选药物。然而，由于POMs在体内代谢较慢而产生了毒副作用，这限制了其在临床上的应用。为了解决此问题，使其与纳米材料组合是一个不错的选择。基于此，本项目研究了基于多钼氧簇的有机改性及其纳米复合材料的设计合成和生物活性。纳米材料用粉末X-射线衍射(PXRD)、傅里叶红外光谱(FT-IR)、X-射线光电子(XPS)能谱、能量色散X-射线(EDX)能谱，扫描电子显微镜(SEM)、透射电子显微镜(TEM)和Zeta电位进行了表征。通过对多钼氧簇纳米复合物抗菌活性和结构的分析，提出了可能的作用方式，包括杂化材料组分与细菌细胞相互作用的潜在靶点，从而为合成功能强大的基于多金属氧酸盐的纳米抗菌剂提供新的机遇。项目成果分别在J. Catal., Int. J. Biol. Macromol., Int. J. Pharmaceut., J. Mater. Chem. B, ACS Biomater. Sci. Eng.,Inorg. Chem., Dalton Trans., Chem. Cat. Chem., J. Inorg. Biochem., Bioorg. Med. Chem. Lett.等国际重要学术期刊上发表SCI收录学术论文30篇；申请国家发明专利6项。该项 目的实施将对缩氨基硫脲及多金属氧簇在药物方面的发展和应用提供实验数据支撑和理论指导。