# Novel Cytotoxic Pt(IV) Compounds with Improved Safety Profiles

**Authors:** Anastasia A. Antonets, Ksenia M. Voroshilkina, Ilya A. Shutkov, Dmitrii M. Mazur, Tatiana P. Serkova, Elena F. Shevtsova, Dmitrii S. Yakovlev, Mariya S. Pshenichnikova, Umida M. Ibragimova, Roman A. Litvinov, Alexander A. Spasov, Elena R. Milaeva, Alexey A. Nazarov

PMC · DOI: 10.3390/ijms27041750 · International Journal of Molecular Sciences · 2026-02-11

## TL;DR

Researchers developed new platinum-based cancer drugs with vitamin E-like structures that are more toxic to cancer cells and less harmful to normal cells.

## Contribution

Incorporating antioxidant ligands into platinum(IV) complexes to improve safety and efficacy.

## Key findings

- Novel platinum(IV) complexes showed higher cytotoxicity than cisplatin in cancer cells.
- The compounds exhibited less toxicity toward normal fibroblast cells.
- Phenolic ligands conferred antioxidant activity, modulating redox processes.

## Abstract

Platinum(II)-based drugs, such as cisplatin, are commonly used to treat various types of cancer. However, their clinical use is limited due to a number of side effects and the development of resistance. To overcome these limitations, researchers have explored the development of platinum(IV) complexes as potential prodrugs that can be selectively activated under physiological conditions. In this study, we have incorporated synthetic analogs of vitamin E into the structure of platinum(IV) complexes to further improve their safety profile. The antioxidant properties of the compounds were evaluated using DPPH and CUPRAC assays, as well as lipid peroxidation inhibition models, revealing that incorporation of phenolic ligands confers pronounced antioxidant activity. Cytotoxicity was assessed towards cancer cell lines using the MTT assay, where the novel complexes showed significantly increased cytotoxic activity compared to cisplatin, while also demonstrating less toxicity toward normal fibroblast cells under the same in vitro conditions. These results suggest that the conjugation of antioxidant ligands to platinum(IV) scaffolds can modulate both redox processes and the biological activity of the resulting complexes. This proposed design strategy has the potential to create more effective platinum-based cancer treatments with enhanced biological characteristics.

## Linked entities

- **Chemicals:** cisplatin (PubChem CID 5460033)

## Full-text entities

- **Genes:** Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 309122] {aka ASM, ASM1, D11S813E}, H1f6 (H1.6 linker histone, cluster member) [NCBI Gene 24438] {aka H1-6, H1.3, H1D, H1f3, H1ft, H1s-4}
- **Diseases:** colorectal carcinoma (MESH:D015179), ototoxicity (MESH:D006311), Cytotoxicity (MESH:D064420), ovarian adenocarcinoma (MESH:D010051), breast adenocarcinoma (MESH:D001943), RDF (MESH:D011906), injury to (MESH:D014947), neurotoxicity (MESH:D020258), lung carcinoma (MESH:D008175), cancer (MESH:D009369), hypoxic (MESH:D002534), acute toxicity (MESH:D000208)
- **Chemicals:** hexane (MESH:D006586), silica (MESH:D012822), pyridine (MESH:C023666), Na (MESH:D012964), 1-octanol (MESH:D020003), C27H42N2O9Pt (-), 2H (MESH:D003903), H6 (MESH:C003027), H2O2 (MESH:D006861), cisplatin (MESH:D002945), H25 (MESH:C039438), trichloroacetic acid (MESH:D014238), phenols (MESH:D010636), acetone (MESH:D000096), MOPS (MESH:C008550), MTT (MESH:C070243), oxalyl chloride (MESH:C092266), Lipid (MESH:D008055), benzonitrile (MESH:C014356), methyl benzoate (MESH:C044605), OH (MESH:C031356), methylglyoxal (MESH:D011765), CO2 (MESH:D002245), L-glutamine (MESH:D005973), diethyl ether (MESH:D004986), Glucose (MESH:D005947), 3,5-di-tert-butyl-4-hydroxyphenylpropionic acid (MESH:C047854), DMSO (MESH:D004121), ROS (MESH:D017382), phenanthrene (MESH:C031181), PBS (MESH:D007854), TBARs (MESH:D017392), H (MESH:D006859), phosphate (MESH:D010710), NH3 (MESH:D000641), Platinum (MESH:D010984), silica gel (MESH:D058428), methanol (MESH:D000432), 3H (MESH:D014316), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (MESH:C010643), 2,6-di-tert-butylphenol (MESH:C035407), 2,2-diphenyl-1-picrylhydrazyl (MESH:C004931), C (MESH:D002244), uracil (MESH:D014498), 3,5-di-tert-butyl-4-hydroxybenzoic acid (MESH:C062323), nitrobenzene (MESH:C036077), vitamin E (MESH:D014810), CH2Cl2 (MESH:D008752), carboxylic acids (MESH:D002264), N (MESH:D009584), Fe (MESH:D007501), decylamine (MESH:C004744), 2-thiobarbituric acid (MESH:C029684), AGEs (MESH:D017127), oxaliplatin (MESH:D000077150), cyclohexane (MESH:C506365), H16 (MESH:C022870), 13C (MESH:C000615229), aniline (MESH:C023650), essential amino acids (MESH:D000601)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Bos taurus (bovine, species) [taxon 9913]
- **Cell lines:** A2780Cis — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_1942), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), A2780 — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_0134), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), RDF — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_U509), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), MCF7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Full text

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## Figures

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940794/full.md

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Source: https://tomesphere.com/paper/PMC12940794