Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer
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2024
Аутори:
Kazimir, AleksandrGötze, Tom
Lönnecke, Peter
Murganić, Blagoje
Mijatović, Sanja
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Maksimović-Ivanić, Danijela
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Hey-Hawkins, Evamarie
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Triple-negative breast cancer (TNBC) poses challenges in therapy due to the absence of target expression such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal
growth factor receptor 2 (HER2). Frequently, the treatment of TNBC involves the combination of several therapeutics. However, an enhanced therapeutic effect can be also achieved within a single molecule. The efficacy of raloxifene can be improved by designing a raloxifene-based hybrid drug bearing a 2,2’-bipyridine moiety (2). Integration of platinum(II), palladium(II), and nickel(II) complexes into
this structure dramatically changed the cytotoxicity. The platinum(II) dichloride complex 3 did not demonstrate any activity, while palladium(II) and nickel(II) dichloride complexes 4 and 5 exhibited
various cytotoxic behavior towards different types of hormone-receptor positive (HR+) cancer and TNBC cell lines. The replacement of the two chlorido ligands in 3‒5 with a dicarbollide (carborate) ion
[C2B9H11]2- resulted in reduced activity of compounds 6, 7, and 8. However, the palladacarborane complex 7 demonstrated higher selectivity towards TNBC. Furthermore, the mechanism of action was
shifted from cytotoxic to explicitly cytostatic with detectable proliferation arrest and accelerated aging, characterized by senescence-associated phenotype of TNBC cells. This study provides valuable insights into the development of hybrid therapeutics against TNBC.
Кључне речи:
TNBC; group 10 metals; metallacarborane; metallodrugs; raloxifeneИзвор:
ChemMedChem, 2024, e202400006-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- DAAD; funding program number: 57440919
- funding program: Research Grants−Bi-national 2019/2020
DOI: 10.1002/cmdc.202400006
ISSN: 1860-7179
PubMed: 38642018