Zia Mohammad Khalid, Siddiqui Tooba, Ali Syed Saqib, Rehman Ahmed Abdur, Ahsan Haseeb, Khan Fahim Halim
Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh, India.
Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India.
Curr Protein Pept Sci. 2018;19(10):937-947. doi: 10.2174/1389203718666171002115547.
In the last few decades, advances in the cancer chemotherapy have been a marked success. A large number of anticancer drugs currently in use include drugs based on platinum complexes such as cisplatin, base analogues such as 5-florouracil and some ruthenium drugs. This review provides a bird's eye view of interaction of a number of clinically important drugs currently in use that show covalent or non-covalent interaction with serum proteins. Platinum drug-cisplatin interacts covalently and alters the function of the key plasma protease inhibitor molecule -alpha-2-macroglobulin and induces the conformational changes in the protein molecule and inactivates it. 5-fluorouracil (5-FU) is extensively metabolized and at physiological concentrations, is found to be associated with Human Serum Albumin (HSA). Similarly ruthenium compounds bind tightly to plasma proteins- serum albumin and serum transferrin, modifying their biological activity and increasing the toxicity of drug to cancer cells. Insight into varied anticancer drug- protein interaction will go a long way in understanding in totality of the mechanism of action of any anticancer drug and its possible effects/side effects.
在过去几十年中,癌症化疗取得了显著进展。目前大量使用的抗癌药物包括基于铂配合物的药物(如顺铂)、碱基类似物(如5-氟尿嘧啶)以及一些钌药物。本综述对目前临床上使用的一些重要药物与血清蛋白的相互作用进行了概述,这些药物表现出与血清蛋白的共价或非共价相互作用。铂类药物顺铂通过共价作用改变关键血浆蛋白酶抑制剂分子——α-2-巨球蛋白的功能,诱导蛋白质分子的构象变化并使其失活。5-氟尿嘧啶(5-FU)在生理浓度下会被广泛代谢,并被发现与人血清白蛋白(HSA)相关。同样,钌化合物与血浆蛋白——血清白蛋白和血清转铁蛋白紧密结合,改变它们的生物活性并增加药物对癌细胞的毒性。深入了解各种抗癌药物与蛋白质的相互作用,对于全面理解任何抗癌药物的作用机制及其可能的效果/副作用具有重要意义。