International Journal of Molecular Sciences, 2014, 15(2):1962-82.

Genistein in 1:1 Inclusion Complexes with Ramified Cyclodextrins: Theoretical, Physicochemical and Biological Evaluation

Corina Danciu, Mircea Oltean, et al

Faculty of Pharmacy, University of Medicine and Pharmacy "Victor Babeş", Eftimie Murgu Square, No. 2, 300041 Timişoara, Romania; et al

Genistein is one of the most studied phytocompound in the class of isoflavones, presenting a notable estrogenic activity and in vitro and/or in vivo benefits in different types of cancer such as those of the bladder, kidney, lung, pancreatic, skin and endometrial cancer. A big inconvenience for drug development is low water solubility, which can be solved by using hydrophilic cyclodextrins. The aim of this study is to theoretically analyze, based on the interaction energy, the possibility of a complex formation between genistein (Gen) and three different ramified cyclodextrins (CD), using a 1:1 molar ratio Gen:CD. Theoretical data were correlated with a screening of both in vitro and in vivo activity. Proliferation of different human cancer cell lines, antimicrobial activity and angiogenesis behavior was analyzed in order to see if complexation has a beneficial effect for any of the above mentioned activities and if so, which of the three CDs is the most suitable for the incorporation of genistein, and which may lead to future improved pharmaceutical formulations. Results showed antiproliferative activity with different IC50 values for all tested cell lines, remarkable antimicrobial activity on Bacillus subtilis and antiangiogenic activity as revealed by CAM assay. Differences regarding the intensity of the activity for pure and the three Gen complexes were noticed as explained in the text. The data represent a proof that the three CDs can be used for furtherer research towards practical use in the pharmaceutical and medical field.

《国际分子科学杂志》，2014年2月

在 1:1 的包合物与分枝状环糊精中的金雀异黄素︰ 理论、 物理化学性能和生物学评估

科瑞娜 丹秀，米尔恰 奥尔滕，等

罗马尼亚维克多医药大学制药学院等

金雀异黄素在异黄酮中是最广泛研究的化合物之一，表现出显著的雌激素活性，并且对不同类型的癌症如膀胱、 肾、 肺、 胰腺、 皮肤和子宫内膜癌等在体外和/或体内发挥作用。药物开发的大难题是水溶解度低，可以利用亲水性环糊精解决。本研究的目的在于从理论上分析，基于相互作用能量，金雀异黄素 （Gen） 和三种不同的分枝环糊精 (CD)，按照Gen︰ CD =1:1的摩尔比形成复合物的可能性。理论数据与体内和体外活性的筛选相关。分析不同人体肿瘤细胞的增殖，抗菌活性及血管生成行为来确认络合物是否有益于上述提到的任何活性，并且如果有益的话，这三种Cd 中最适合被纳入金雀异黄素中的一个可能会导致未来药剂配方的改进。结果表明具有不同IC50 值的所有测试的细胞株抗增殖活性，对枯草芽孢杆菌显著的抗菌活性和通过CAM测试得到的抗血管生成活性。在本文中描述了三种Gen配合物和活性强度的差异。当前的数据表明三 种Cd 可被用于进一步研究其在医药和医疗领域的实际应用。