Abid Mohammad, Shamsi Farheen, Azam Amir
Department of Chemistry, Faculty of Natural Sciences, Jamia Millia Islamia University, P.O. Box: 110025, New Delhi, India.
Mini Rev Med Chem. 2016;16(10):772-86. doi: 10.2174/1389557515666151001142012.
GLOBOCAN 2012 estimates 14.1 million new cancer cases and 8.2 million cancer-related deaths worldwide. Cancer is rapidly becoming a major public health concern in India as well, with the number of new cancer cases anticipated to double within the next 20 years. The percentage of currently approved metallodrugs is very low, in contrast to the majority of drugs available as organic compounds. The search for alternative drugs to cisplatin, carboplatin and other derivatives is highly needed due to their severe side effects including nephrotoxicity and neurotoxicity. Ruthenium, among other transition metal complexes appears to be a possible candidate for cancer therapy in the near future. The most significant rationale is ruthenium's octahedral chemistry and greater propensity to undergo redox reactions. The hypoxic environment of tumors favors the reduction of inert ruthenium (III) to active ruthenium (II) which opens new prospects for the development of novel prodrugs. Although studies suggest that ruthenium complexes penetrate well within the tumor cells and bind effectively to DNA, its binding to proteins is not very well explained. Ruthenium complexes are presently receiving great attention in the fields of biological, pharmaceutical and medicinal chemistry as anticancer agents. This review poses a comprehensive overview of the studies on competent anticancer ruthenium complexes and the role of these metal complexes in relation to their anticancer properties as well as those under clinical trials.
《全球癌症报告》2012年估计,全球有1410万新增癌症病例和820万癌症相关死亡病例。癌症在印度也正迅速成为一个主要的公共卫生问题,预计未来20年内新增癌症病例数量将翻倍。与大多数有机化合物类药物相比,目前已获批的金属药物所占比例非常低。由于顺铂、卡铂及其他衍生物具有包括肾毒性和神经毒性在内的严重副作用,因此迫切需要寻找替代药物。在其他过渡金属配合物中,钌在不久的将来似乎是癌症治疗的一个可能候选物。最重要的原因是钌的八面体化学性质以及更容易发生氧化还原反应。肿瘤的缺氧环境有利于将惰性的钌(III)还原为活性的钌(II),这为新型前药的开发开辟了新前景。尽管研究表明钌配合物能很好地渗透到肿瘤细胞内并有效地与DNA结合,但其与蛋白质的结合情况还不是很清楚。目前,钌配合物作为抗癌剂在生物、制药和药物化学领域受到了极大关注。本综述全面概述了有关活性抗癌钌配合物的研究,以及这些金属配合物在抗癌特性方面的作用以及正在进行临床试验的情况。