In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors
2023
Аутори:
Braun, SebastianPaskaš, Svetlana
Laube, Markus
George, Sven
Hofmann, Bettina
Lönnecke, Peter
Steinhilber, Dieter
Pietzsch, Jens
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey‐Hawkins, Evamarie
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. Here, the first carborane-containing dual COX-2/5-LO inhibitors derived from RWJ-63556 are presented. The replacement of the fluorophenyl moiety by meta- or para-carborane resulted in five carborane-containing derivatives 3, 6, 9, 13, and 17 that show high inhibitory activities toward COX-2 and 5-LO in vitro. Cell viability studies on the A375 melanoma cell line revealed that meta-carborane derivative 3 shows higher anticancer activity compared to RWJ-63556 based on accumulation of lipid droplets in the cells due to blockage of the COX-2 and 5-LO pathways, indicating a promising approach for the design of potent dual COX-2/5-LO inhibitors.
Кључне речи:
bioisosteric replacement; cancer; carboranes; cyclooxygenases; dual inhibitors; lipoxygenases; multitarget drugsИзвор:
Advanced Therapeutics, 2023, 2200252-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)
- Deutsche Forschungsgemeinschaft (SFB 1039)
- Graduate School Leipzig School of Natural Sciences ‐ Building
DOI: 10.1002/adtp.202200252
ISSN: 2366-3987
WoS: 000906458200001
Scopus: 2-s2.0-85145476935
URI
https://onlinelibrary.wiley.com/doi/10.1002/adtp.202200252http://radar.ibiss.bg.ac.rs/handle/123456789/5384