Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes
Аутори
Kazimir, AleksandrSchwarze, Benedikt
Lönnecke, Peter
Jelača, Sanja
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for tripl...e-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.
Кључне речи:
breast cancer / cytotoxicity / oxidative stress / palladacarboranes / palladium dichloride / platinacarboranes / platinum dichloride / tamoxifen derivativeИзвор:
Pharmaceutics, 2023, 15, 2, 682-Издавач:
- MDPI
Финансирање / пројекти:
- Deutscher Akademischer Austauschdienst (DAAD; funding program number: 57440919; funding program: Research Grants−Bi-national 2019/2020)
- 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)
Напомена:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/5893
Повезане информације:
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Kazimir, Aleksandr AU - Schwarze, Benedikt AU - Lönnecke, Peter AU - Jelača, Sanja AU - Mijatović, Sanja AU - Maksimović-Ivanić, Danijela AU - Hey-Hawkins, Evamarie PY - 2023 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5892 AB - The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities. PB - MDPI T2 - Pharmaceutics T1 - Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes VL - 15 IS - 2 SP - 682 DO - 10.3390/pharmaceutics15020682 ER -
@article{ author = "Kazimir, Aleksandr and Schwarze, Benedikt and Lönnecke, Peter and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie", year = "2023", abstract = "The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.", publisher = "MDPI", journal = "Pharmaceutics", title = "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes", volume = "15", number = "2", pages = "682", doi = "10.3390/pharmaceutics15020682" }
Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics MDPI., 15(2), 682. https://doi.org/10.3390/pharmaceutics15020682
Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics. 2023;15(2):682. doi:10.3390/pharmaceutics15020682 .
Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes" in Pharmaceutics, 15, no. 2 (2023):682, https://doi.org/10.3390/pharmaceutics15020682 . .