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选择性有机金属化合物作为具有新型作用模式的抗癌药物候选物的开发和未来前景。

Development and future prospects of selective organometallic compounds as anticancer drug candidates exhibiting novel modes of action.

机构信息

Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, India.

Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, India.

出版信息

Eur J Med Chem. 2019 Aug 1;175:269-286. doi: 10.1016/j.ejmech.2019.04.062. Epub 2019 May 1.

Abstract

Organometallic complexes have widely been used for the treatment of various diseases viz., malaria, arthritis, syphilis, pernicious anemia, tuberculosis and particular in cancers. Recent decades have witnessed an upsurging interest in the application of organometallic compounds to treat various phenotypes of cancers with multiple etiologies. The unique and exceptional properties of organometallic compounds, intermediate between classical inorganic and organic materials provide new insight in the progress of inorganic medicinal chemistry. Herein, we have selectively focused on various organometallic sandwich and half-sandwich complexes of ruthenium (Ru), titanium (Ti), gold (Au) and iron (Fe) exhibiting promising activity towards a panel of cancer cell lines and resistant cancer cell lines. These complexes exhibit novel mechanisms of drug action through incorporation of outer-sphere recognition of molecular targets and controlled activation features based on ligand substitution along with monometallic and heterometallic redox processes. Furthermore, they are usually found to be uncharged or neutral possessing metals in a low oxidation state, exhibit kinetic stability, relative lipophilicity and are amenable to a host of various chemical transformations. This review mainly sheds light on the successful advancement of organometallic complexes as anticancer drug aspirants in relation to their versatile structural chemistry and innovative mechanisms of action targeting nucleic acids, several enzymes viz; thioredoxin reductases (Thrx), EGFR, transferrin, cathepsin B, topoisomerases etc.

摘要

金属有机配合物已广泛用于治疗各种疾病,如疟疾、关节炎、梅毒、恶性贫血、结核病和癌症。近几十年来,人们对应用金属有机化合物治疗具有多种病因的各种癌症表型产生了浓厚的兴趣。金属有机化合物具有介于经典无机和有机材料之间的独特和特殊性质,为无机药物化学的发展提供了新的见解。在这里,我们选择性地关注了各种钌(Ru)、钛(Ti)、金(Au)和铁(Fe)的金属有机夹心和半夹心配合物,这些配合物对一系列癌细胞系和耐药癌细胞系表现出有希望的活性。这些配合物通过结合分子靶标的外球识别和基于配体取代的控制激活特性以及单金属和异金属氧化还原过程,表现出新颖的药物作用机制。此外,它们通常为不带电或中性的,具有低氧化态的金属,表现出动力学稳定性、相对亲脂性,并适合进行多种化学转化。本综述主要介绍了金属有机配合物作为抗癌药物候选物的成功进展,重点介绍了它们针对核酸、多种酶(如硫氧还蛋白还原酶(Thrx)、表皮生长因子受体、转铁蛋白、组织蛋白酶 B、拓扑异构酶等)的多功能结构化学和创新作用机制。

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