On the Mechanism of Action of the Antitumor Drug cis‐Platin(cis‐DDP) and its Second Generation Derivatives

Abstract

Abstract-The present article attempts to summarise the elements of the mechanism of action of the antitumor drug ci___s-Pl ati n presented the Iast few years. Highlights on the discovery of the drug and the development of it's second generation derivatives are presented, as well as the ways that cis___-DDP reacts with biomolecules as DNA and proteins and their models e.g. nucleosides, nucleotides.Also the hydrolysis data are presented for ci__s-DDP and its' inactive congener trans-DDP, as well as for the second generation drug carboplatin. Finally, useful l conclusions are given from this work, pointing out the unanswered questions about the action of cis-DDP as well as its differences in action, in comparison with trans-DDP.

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

“…The potential increases in the positive direction as the degree of ionization increases. In attachment to DNA, inner sphere complexes exhibit covalent binding, whereas outer sphere types are characterized by ionic bonds [132], which should influence ET properties.…”

Chemotherapy induced immunogenic cell death alters response to exogenous activation of STING pathway and PD-L1 immune checkpoint blockade in a syngeneic murine model of ovarian cancer

“…Carboplatin and doxorubicin, elicit their cancer cell killing effects via distinct modes of action. For example, carboplatin functions by eliciting DNA damage to block replicative machinery and ultimately causes the cell to undergo apoptosis while doxorubicin intercalates with DNA to inhibit topoisomerase II function and produces a high level of reactive oxygen species leading to membrane damage 34, 35 . While both are known to induce ICD, they achieve cell death through differing molecular mechanisms resulting in varying levels of ICD.…”

DNA interaction of dioxycyclobutenedione- (1,2-cyclohexanediamine) platinum(II) complex with potential anticancer activity

“…It has been replaced later by its derivative cis-diammine-[1,1-cyclobutane-dicaboxylate-(2)-O,O 0 ] platinum(II), called carboplatin for its better performance in pharmokokinetics, and less toxicity [1][2][3]. Today, as the third generation of the drug with better efficiency and less toxicity, thousands of cis-platinum analogs have been synthesized and evaluated for their structure and activity relationship [4][5][6][7].…”