REQUIMTE, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, s/n, Rua do Campo Alegre, 4169-007 Porto, Portugal.
Recent Pat Anticancer Drug Discov. 2013 May;8(2):168-82. doi: 10.2174/1574892811308020005.
In this review, we discuss the current patents concerning aryl/heteroaryl thiosemicarbazone derivatives as regards to their activities and properties, including coordination (chelation) properties. The mode of action of the aryl/heteroaryl thiosemicarbazone derivatives involves metal coordination with proteins or biological fluids that have metal ions in their structure. Additionally, these molecules can also form multiple hydrogen bonds through their (thio) amide and N3 nitrogen that ensure a strong interaction with the receptor. In some cases, strong π-π interactions can be observed too. Special attention is given to pyridyl, bis-pyridyl, benzoylpyridyl and isatin thiosemicarbazone derivatives that exhibit significant anticancer, antiviral and other activities in free and in metal complexed forms. This key biological role is often related with their capability to inhibit the enzyme ribonucleotide reductase, similar to what is observed with potent anticancer drugs such as Triapine and methisazone. Recent studies have revealed that thiosemicarbazone can also inhibit topoisomerase II α enzyme. Thiosemicarbazone derivatives form coordination complex with various metals such as Zn, Cu, Fe, Co, Ni, Pt, Pd, etc., and these complexes provide better activities than the free thiosemicarbazones. Recent patents show that the controlled or sustained release dosage form of the thiosemicarbazone derivatives along with ionizing radiations is used for the treatment of proliferative diseases (US20110152281, US20110245304, US20120172217).
在这篇综述中，我们讨论了芳基/杂芳基缩氨硫脲衍生物的现有专利，涉及它们的活性和性质，包括配位（螯合）性质。芳基/杂芳基缩氨硫脲衍生物的作用模式涉及金属与蛋白质或生物流体的配位，这些蛋白质或生物流体的结构中含有金属离子。此外，这些分子还可以通过其（硫）酰胺和 N3 氮形成多个氢键，从而确保与受体的强相互作用。在某些情况下，也可以观察到强的π-π相互作用。特别关注吡啶基、双吡啶基、苯甲酰基吡啶基和色酮缩氨硫脲衍生物，它们以游离形式和金属络合物形式表现出显著的抗癌、抗病毒和其他活性。这种关键的生物作用通常与它们抑制核酶核糖核苷酸还原酶的能力有关，类似于三嗪和甲替唑啉等强效抗癌药物。最近的研究表明，缩氨硫脲还可以抑制拓扑异构酶 IIα 酶。缩氨硫脲衍生物与各种金属（如 Zn、Cu、Fe、Co、Ni、Pt、Pd 等）形成配位络合物，这些络合物比游离缩氨硫脲具有更好的活性。最近的专利表明，缩氨硫脲衍生物的控释或缓释剂型与电离辐射一起用于治疗增殖性疾病（US20110152281、US20110245304、US20120172217）。
