RETRACTED: Pt(IV) Bifunctional Prodrug Containing 2-(2-Propynyl)octanoato Axial Ligand: Induction of Immunogenic Cell Death on Colon Cancer

Abstract

The synthesis, characterization, and in vitro activity of a cyclohexane-1R,2R-diamine-based Pt(IV) derivative containing the histone deacetylase inhibitor rac-2-(2-propynyl)octanoato, namely, (OC-6-44)-acetatodichlorido(cyclohexane-1R,2R-diamine)-(rac-2-(2-propynyl)octanoato)platinum(IV), are reported together with those of its isomers containing enantiomerically enriched axial ligands. These Pt(IV) complexes showed comparable activity, of 2 orders of magnitude higher than reference drug oxaliplatin on three human (HCT 116, SW480, and HT-29) and one mouse (CT26) colon cancer cell lines. In vivo experiments were carried out on immunocompetent BALB/c mice bearing the same syngeneic tumor. The complex (OC-6-44)acetatodichlorido(cyclohexane-1R,2R-diamine)(rac-2-(2-propynyl)octanoato)platinum(IV) showed higher tumor mass Pt accumulation than oxaliplatin, due to its higher lipophilicity, with negligible nephro-and hepatotoxicities when administered intravenously. A remarkable tumor mass invasion by cytotoxic CD8 + T lymphocytes, following the Pt(IV) treatment, indicated a strong induction of immunogenic cell death.

Theoretical Prediction of Dual-Potency Anti-Tumor Agents: Combination of Oxoplatin with Other FDA-Approved Oncology Drugs

“…Despite increasing interest in the possible associations between oxoplatin and other drugs [ 41 , 42 , 43 , 44 , 45 , 46 ], there is currently no recommended approach to systematically improving the anti-cancer activity of bifunctional drugs based on Pt(IV). With the aim of contributing to the design of enhanced anti-cancer drugs, we used a state-of-the-art computational approach to screen the latest FDA-approved oncology drugs.…”

Monofunctional Platinum(II) Anticancer Agents

“…Generally, Pt drugs induce cancer cell death by interfering with DNA synthesis or causing chemical damage to DNA, which is mainly manifested by apoptosis. However, accumulating evidences indicate that Pt drugs may have other molecular targets in addition to DNA, which can induce cell death through non-apoptotic pathways, such as autophagy, necrosis, and even immunogenicity [105,[120][121][122][123]. Complexes 44-46 ( Figure 16) showed a dose-dependent antiproliferative activity in the A2780 cells, with the cytotoxicity order of 44 < 45 < 46, by a combinative apoptotic mechanism involving mitochondrial and autophagic pathways [124].…”

An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer

“…Sabbatini et al. found that a Pt IV prodrug containing a 2‐(2‐propyl) octanol axial ligand‐induced ICD in colon cancer [27] . Kaur et al.…”

“…[26] Sabbatini et al found that aPt IV prodrug containing a2-(2-propyl) octanol axial ligandinduced ICD in colon cancer. [27] Kaur et al reported acopper-(II) complex containing apolypyridyl ligand and aSchiff base ligand had the capable of inducing ICD in breast cancer stem cells. [28] Ding et al proved MnOx Nanospikes induced ICD by chemodynamic therapy (CDT) and ferroptosis.…”