CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway
2017
Аутори:
Kuhnert, RobertSárosi, Menyhárt-Botond
George, Sven
Lönnecke, Peter
Hofmann, Bettina
Steinhilber, Dieter
Murganić, Blagoje
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Тип документа:
Чланак у часопису (Објављена верзија)
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Метаподаци
Приказ свих података о документуАпстракт:
The progression of cancer is accelerated by increased proliferation, angiogenesis, and inflammation. These processes are mediated by leukotrienes. Several cancer cell lines overexpress 5-lipoxygenase, an enzyme that converts arachidonic acid into leukotrienes. An early inhibitor of the 5-lipoxygenase pathway is Rev-5901, which, however, lacks in invivo efficacy, as it is rapidly metabolized. We investigated the introduction of carboranes as highly hydrophobic and metabolically stable pharmacophores into lipoxygenase inhibitors. Carboranes are icosahedral boron clusters that are remarkably stable and used to increase the metabolic stability of unstable pharmaceutics without changing their biological activity. By introduction of meta-carborane into Rev-5901, the first carborane-based inhibitor of the 5-lipoxygenase pathway was obtained. We report the synthesis and inhibitory and cytotoxic behavior of these compounds toward several melanoma and colon cancer cell lines and their related anticancer mechanisms.
Кључне речи:
Aasthma; Cancer; Carboranes; Inhibitors; LipoxygenaseИзвор:
ChemMedChem, 2017, 12, 13, 1081-1086Финансирање / пројекти:
- Молекуларни механизми физиолошке и фармаколошке контроле инфламације и канцера (RS-MESTD-Basic Research (BR or ON)-173013)
- Deutsche Forschungsgemeinschaft. Grant Numbers: HE 1376/38-1, SFB 1039, SA 2902/2-1
- Fonds der Chemischen Industrie
- European Social Fund
- Graduate School Leipzig School of Natural Sciences - Building with Molecules and Nano-objects (BuildMoNa)
- Else Kröner-Fresenius Foundation
DOI: 10.1002/cmdc.201700309
ISSN: 1860-7179
PubMed: 28569429