以铂为基础的癌症化疗药物:近期趋势和未来展望

S. Parveen
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引用次数: 1

摘要

铂基药物已被证明是无机药物化学领域的普遍成功之一。到目前为止,市场上已经出现了三代铂类药物,并被认为在治疗各种类型的肿瘤中发挥着关键作用。世界范围内最常用的抗癌化疗药物是顺铂、奥沙利铂和卡铂。众所周知,它们表现出突出而有趣的化学治疗效果。然而,由于脱靶活性引发的严重副作用以及某些癌症类型获得性/内在耐药导致的疗效降低,铂化疗在变革性临床实施中可能受到限制。顺便提一下,20世纪80年代末最初研究的带有一个不稳定配体的单功能铂复合物再次引起了人们的关注。与具有两种不稳定配体的双功能抗癌复合物相比,即通过形成链间和链内交联而在DNA链中产生扭曲的顺铂,单功能Pt(II)复合物被发现通过一个离开氯基团所显示的单独配位位点与DNA结合。然而,迄今为止,还没有其他非铂类金属抗癌药物能够有效地通过临床试验的所有阶段。因此,寻找新的基于pt的抗癌药物正在积极进行,因为它们仍然在几乎50%的癌症患者的化疗谱中发挥主要作用。与此同时,寻找新的铂化疗药物的主要目标是:a)开发它们的潜力,b)避免不良的副作用,c)治愈耐药肿瘤,d)完善细胞药代动力学机制。这篇小型综述强调了生产下一代Pt抗癌药物的众多持续努力。
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Platinum-based cancer chemotherapeutics: Recent trends and future perspectives
Platinum-based drugs have been proved as one of the prevalent successes in the field of inorganic medicinal chemistry. So far, three generations of platinum-based drugs are in the market and are recognized to play critical roles in the treatment of various types of tumors. The most commonly used anticancer chemotherapeutics worldwide are particularly cisplatin, oxaliplatin, and carboplatin. They are known to exhibit prominent and interesting chemo-therapeutic effects. Nevertheless, Pt chemotherapy can be limited in transformative clinical implementation owing to the severe side effects triggered by off-target activity and lowered efficacy because of acquired/intrinsic resistance in some cancer types. Incidentally, monofunctional Pt complexes, those bearing one labile ligand, initially studied in the late 1980s, are again enticing renewed attention. in comparison to the bifunctional anticancer complexes, bearing two labile ligands, viz., cisplatin which creates a distortion in the DNA strands by forming inter-and intrastrand crosslinks, monofunctional Pt(II) complexes were found to exclusively bind to DNA via a solo coordination site revealed by the one leaving chloride group. However, till date, no other non-platinum metal-based anticancer drug has been able to efficaciously pass all stages of clinical trials. Hence, the hunt for novel Pt-based anticancer drug is being pursued vigorously for the reason that they still play a principal role in the chemotherapeutic profiles of almost 50% of all cancer patients. Meanwhile, the major significant goals in the search for new Pt chemotherapeutic drugs is to focus- a) on exploiting their potential, b) averting the undesirable side effects, c) in curing resistant tumors, and d) in refining the cellular pharmacokinetic regimes. This mini review highlights the numerous continuing efforts to produce the next generation of Pt anticancer drugs.
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