金属基络合物在许多慢性疾病的治疗中占据了开创性的地位,包括各种类型的癌症。尽管顺铂治疗许多实体恶性肿瘤取得了惊人的成功,迄今为止,临床上用于抗癌化疗的金属药物数量有限。虽然许多其他突出的铂和非铂基金属药物(例如NAMI-A,KP1019,卡铂,奥沙利铂,二氯化二茂钛,casiopeinas®等)已进入临床试验,由于有害的毒性作用,许多人在研发的后期阶段失败了,固有耐药性和不良的药代动力学反应以及低疗效。尽管如此,多年来,药物无机化学领域的研究呈指数级增长,采用新的基于靶标的药物设计策略,旨在改善药理学结果,同时减轻这些药物实体的副作用。在过去的几十年里,天然产物成为抗癌药物开发的关键结构基序之一。药物化学领域的许多杰出研究人员致力于开发新的3d过渡金属基抗癌药物/重新利用现有的生物活性化合物,这些化合物来自多种药效团,如香豆素,黄酮类化合物,色原,生物碱等.天然生物碱及其类似物的金属配合物,jatrorrhizine,小檗碱,氧杂吗啡,8-羟基喹啉等.在抗癌药物开发过程中获得了突出的地位,因为天然存在的生物碱可以抗增殖,诱导细胞凋亡,抑制血管生成,具有较好的愈合效果。虽然它们中的一些是ERK信号调节激酶的抑制剂,其他显示基于环氧合酶-2(COX-2)和端粒酶抑制的活性。然而,这些生物碱复合物的靶标仍不清楚,尽管已经确定它们通过在体外和体内干扰肿瘤发生和肿瘤进展的多种途径而证明了抗癌效力。在过去的十年里,在开发基于天然生物碱的金属药物治疗以干预癌症化疗方面取得了许多重大进展,这些进展总结如下,并在本文中进行了综述。
Metal-based complexes have occupied a pioneering niche in the treatment of many chronic diseases, including various types of cancers. Despite the phenomenal success of cisplatin for the treatment of many solid malignancies, a limited number of metallo-drugs are in clinical use against cancer chemotherapy till date. While many other prominent platinum and non‑platinum- based metallo-drugs (e.g. NAMI-A, KP1019, carboplatin, oxaliplatin, titanocene dichloride, casiopeinas® etc) have entered clinical trials, many have failed at later stages of R&D due to deleterious toxic effects, intrinsic resistance and poor pharmacokinetic response and low therapeutic efficacy. Nonetheless, research in the area of medicinal inorganic chemistry has been increasing exponentially over the years, employing novel target based drug design strategies aimed at improving pharmacological outcomes and at the same time mitigating the side-effects of these drug entities. Over the last few decades, natural products became one of the key structural motifs in the anticancer drug development. Many eminent researchers in the area of medicinal chemistry are devoted to develop new 3d-transition metal-based anticancer drugs/repurpose the existing bioactive compounds derived from myriad pharmacophores such as coumarins, flavonoids, chromones, alkaloids etc. Metal complexes of natural alkaloids and their analogs such as luotonin A, jatrorrhizine, berberine, oxoaporphine, 8-oxychinoline etc. have gained prominence in the anticancer drug development process as the naturally occurring alkaloids can be anti-proliferative, induce apoptosis and exhibit inhibition of angiogenesis with better healing effect. While some of them are inhibitors of ERK signal-regulated kinases, others show activity based on cyclooxygenases-2 (COX-2) and telomerase inhibition. However, the targets of these alkaloid complexes are still unclear, though it is well-established that they demonstrate anticancer potency by interfering with multiple pathways of tumorigenesis and tumor progression both in vitro and in vivo. Over the last decade, many significant advances have been made towards the development of natural alkaloid-based metallo-drug therapeutics for intervention in cancer chemotherapy that have been summarized below and reviewed in this article.