ADVANCES IN METAL-BASED ANTICANCER DRUGS: CHEMISTRY OF PLATINUM, GOLD, AND RUTHENIUM COMPLEXES AS CHEMOTHERAPEUTIC AGENTS

Abstract

Metal-based anticancer agents are some of the important chemotherapeutic agents used to work for different mechanisms of actions affecting tumor cells. The article indicates the cytotoxicity, studies on the interaction of DNA, and in vivo efficacy of platinum, gold, and ruthenium complexes. The platinum compounds with dipyridoquinoxaline (dpq) ligands were proved to be highly cytotoxic that particularly showed maximum activity in drug-resistant ovarian cancer models, where it outperformed carboplatin with better DNA intercalation into DNA and induction of apoptosis. Gold complexes such as Auoxo6 and Au2phen were more cytotoxic against both colorectal and ovarian cancer cells because of their mitochondrial targeting and ROS-dependent apoptosis.The ruthenium complexes KP1019 and NAMI-A were taken up selectively into the tumor tissues, in which they seemed to selectively initiate oxidative stress responses and apoptosis. DNA binding and cleavage assays further confirmed the ability of the platinum and ruthenium complexes to induce structural DNA damage, whereas mitochondrial DNA was targeted selectively by the gold complexes, thereby obstructing cellular energy production. The in vivo models displayed a dramatic tumor growth inhibition in which platinum and gold complexes exhibited 60% inhibition of tumor size in the resistant model. Combinations of platinum and ruthenium complexes have shown synergistic effects on the apoptosis of multidrug-resistant cancers. Again, these results manifest the potential of metal-based drugs as chemoresistance antagonists, thereby allowing the development of hybrid strategies, which include nanoparticle formulations and immunomodulatory regimens, to increase therapeutic efficacy. Future research endeavors focusing on ligand design, targeted delivery, and combinations of therapy will lead to more refinement of these agents for their further application in oncology. .