Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
Laboratorio de Biología Celular, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, México.
FEBS Open Bio. 2022 May;12(5):880-899. doi: 10.1002/2211-5463.13381. Epub 2022 Apr 5.
Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well-established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt-N via coordination of the inhibition of enzymes); (b) redox-active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti-invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs.
癌症是一种异质性和多因素的疾病,在全球范围内导致高死亡率;因此,找到最有效的治疗方法是一个主要的研究挑战。目前,大多数抗癌药物只有少数几个确立的靶点,如细胞增殖或死亡;然而,重要的是要考虑到癌症向病理阶段的恶化意味着侵袭和转移过程。药用无机化学(MIC)是一个新兴的领域,涉及新无机化合物的设计、合成、表征、临床前评价和作用机制的研究,这些新化合物被称为金属药物。金属离子的性质允许丰富的设计新药物的策略,从而调整物理化学和立体化学性质。金属药物可以采用四面体、八面体、正方形平面和正方形平面金字塔等几何形状,调整其排列方式,并有利于与各种靶标结合。一些金属离子的氧化还原性质可以通过结合配体来调节,从而调整其相互作用,从而开辟一系列作用机制。在这方面,触发金属药物生物活性的作用机制通常通过以下几种方式确定:(a)金属与生物分子的配位(例如,顺铂与 DNA 鸟嘌呤的 N7 配位,形成 Pt-N 通过抑制酶的配位);(b)氧化还原活性;和(c)ROS 产生。因此,一系列金属药物可以与癌症侵袭过程中的几个特定靶标相互作用,并预防转移。一些金属化合物的结构基础通过抑制与癌症进展相关的信号通路显示出巨大的抗癌潜力。在这篇综述中,我们介绍了金属药物在抗转移作用方面的研究进展。