Ndagi Umar, Mhlongo Ndumiso, Soliman Mahmoud E
Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa.
Drug Des Devel Ther. 2017 Mar 3;11:599-616. doi: 10.2147/DDDT.S119488. eCollection 2017.
In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective targeting remains the hope of the future in developing therapeutics that would selectively target cancer cells and leave healthy cells unharmed.
过去，金属基化合物被广泛用于疾病治疗，但治疗剂量和毒性剂量缺乏明确区分是一个重大挑战。1960年巴尼特·罗森伯格发现顺铂，见证了金属基化合物用于癌症治疗历史上的一个里程碑。这为金属基抗癌药物的现代时代奠定了基础。顺铂、卡铂和奥沙利铂等铂类药物是金属基化合物治疗癌症的中流砥柱，但其他金属基化合物治疗效果的延迟阻碍了该领域的研究进展。然而，最近，基于结构信息的研究活动激增，旨在改进和开发其他形式的金属基化合物以及非经典铂配合物，其作用机制不同于顺铂等已知药物。与此一致，通过配体取代重新设计现有化学结构或构建具有更高安全性和细胞毒性特征的全新化合物，已经合成了更多的金属基化合物。然而，由于越来越强调金属基配合物的临床相关性，目前这些药物中有少数正在进行临床试验，还有更多正在等待伦理批准以加入试验。在本综述中，我们试图概述以前关于金属基配合物细胞毒性作用的综述，同时更多地关注新设计的金属基配合物及其对癌细胞系的细胞毒性作用，以及金属基药物设计的新方法和癌症治疗中的分子靶点。我们乐观地认为，选择性靶向的概念仍然是未来开发能够选择性靶向癌细胞而不伤害健康细胞的治疗方法的希望所在。
