Guzowska Magdalena, Kalinowska Monika, Lewandowski Wlodzimierz
Warsaw University of Life Sciences - SGGW, Faculty of Veterinary Medicine, Department of Physiological Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland.
Bialystok University of Technology, Division of Chemistry, Faculty of Civil Engineering and Environmental Engineering, Wiejska 45E, 15-351 Bialystok, Poland.
Anticancer Agents Med Chem. 2018;18(4):476-487. doi: 10.2174/1871520618666171129213132.
The constant search for successful cancer therapies lasts for decades. Apart from the huge scientific effort and enormous sum of spent money, only a small amount of newly developed medicines move into clinical use (only 94 registered anticancer drugs in the last 12 years). Anticancer regimes are still overcome by drugs invented over 50 years ago such as cisplatin and doxorubicin. Significant progress in the development of improved anticancer drugs was made due to multiple studies on the relationship between the molecular structure of chemical compounds and their cytostatic activity. A number of ligands (mainly organic) with quite effective anticancer properties are known, but they show insufficient activity, selectivity and multidrug resistance. Formation of transition metal - ligand complexes (with proven anticancer effect) changes the properties of the latter. The factors that affect the cytotoxic properties of metal complexes are: the type of ligand and metal, the nature of the connection between metal and ligand, and the distribution of electronic charge density in the formed complexes. Here, we report the recent efforts to improve existing compounds with confirmed anticancer activity. They seem to be unappreciated as their effects appear to be less spectacular than that of targeted anticancer drugs (i.e. based on antibodies or small RNAs).
对成功的癌症治疗方法的持续探索已经持续了数十年。除了巨大的科研投入和巨额资金花费外，只有少量新开发的药物进入临床使用（在过去12年中仅有94种注册抗癌药物）。抗癌方案仍然被50多年前发明的药物如顺铂和阿霉素所主导。由于对化合物分子结构与其细胞抑制活性之间关系的多项研究，在改进抗癌药物的开发方面取得了重大进展。已知许多具有相当有效抗癌特性的配体（主要是有机配体），但它们的活性、选择性和多药耐药性不足。形成具有已证实抗癌作用的过渡金属-配体配合物会改变后者的性质。影响金属配合物细胞毒性性质的因素包括：配体和金属的类型、金属与配体之间连接的性质以及所形成配合物中电子电荷密度的分布。在此，我们报告了近期为改进具有已证实抗癌活性的现有化合物所做的努力。它们似乎未得到重视，因为其效果似乎不如靶向抗癌药物（即基于抗体或小RNA的药物）那样显著。
