Chemotherapeutic Drugs and Plasma Proteins: Exploring New Dimensions

Abstract

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.

Keywords: 5-FU; Alpha-2-macroglobulin; chemotherapeutic drugs; cisplatin; new dimensions; plasma proteins..