Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer
Аутори
Kazimir, AleksandrGötze, Tom
Murganić, Blagoje
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action again...st TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells.
Извор:
RSC Medicinal Chemistry, 2024Финансирање / пројекти:
- Deutscher Akademischer Austauschdienst [57440919; funding program: Research Grants Bi-national]
Колекције
Институција/група
VinčaTY - JOUR AU - Kazimir, Aleksandr AU - Götze, Tom AU - Murganić, Blagoje AU - Mijatović, Sanja AU - Maksimović-Ivanić, Danijela AU - Hey-Hawkins, Evamarie PY - 2024 UR - https://vinar.vin.bg.ac.rs/handle/123456789/13242 AB - Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells. T2 - RSC Medicinal Chemistry T1 - Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer DO - 10.1039/D4MD00051J ER -
@article{ author = "Kazimir, Aleksandr and Götze, Tom and Murganić, Blagoje and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie", year = "2024", abstract = "Raloxifene, a selective oestrogen receptor modulator (SERM), has demonstrated efficacy in the prevention and therapy of oestrogen receptor-positive (ER+) breast cancer, with some degree of effectiveness against triple-negative forms. This suggests the presence of oestrogen receptor-independent pathways in raloxifene-mediated anticancer activity. To enhance the potential of raloxifene against the most aggressive breast cancer cells, hybrid molecules combining the drug with a metal chelator moiety have been developed. In this study, we synthetically modified the structure of raloxifene by incorporating a 2,2′-bipyridine (2,2′-bipy) moiety, resulting in [6-methoxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl]-[4-(2,2′-bipyridin-4′-yl-methoxy)phenyl]methanone (bipyraloxifene). We investigated the cytotoxic activity of both raloxifene and bipyraloxifene against ER+ breast adenocarcinomas, glioblastomas, and a triple-negative breast cancer (TNBC) cell line, elucidating their mode of action against TNBC. Bipyraloxifene maintained a mechanism based on caspase-mediated apoptosis but exhibited significantly higher activity and selectivity compared to the original drug, particularly evident in triple-negative stem-like MDA-MB-231 cells.", journal = "RSC Medicinal Chemistry", title = "Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer", doi = "10.1039/D4MD00051J" }
Kazimir, A., Götze, T., Murganić, B., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2024). Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer. in RSC Medicinal Chemistry. https://doi.org/10.1039/D4MD00051J
Kazimir A, Götze T, Murganić B, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer. in RSC Medicinal Chemistry. 2024;. doi:10.1039/D4MD00051J .
Kazimir, Aleksandr, Götze, Tom, Murganić, Blagoje, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer" in RSC Medicinal Chemistry (2024), https://doi.org/10.1039/D4MD00051J . .