Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity
2022
Аутори:
Kuhnert, RobertKuhnert, Lydia
Sárosi, Menyhárt‐B.
George, Sven
Drača, Dijana
Paskaš, Svetlana
Hofmann, Bettina
Steinhilber, Dieter
Honscha, Walther
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
12-Lipoxygenase is crucial for tumour angiogenesis. 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon-based pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta-carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).
Кључне речи:
Cancer; Carboranes; Inflammation; Inhibitors; LipoxygenaseИзвор:
ChemMedChem, 2022, 17, 1, e202100588-
DOI: 10.1002/cmdc.202100588
ISSN: 1860-7179
PubMed: 34694057
WoS: 000717008500001
Scopus: 2-s2.0-85118884766
URI
https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202100588http://radar.ibiss.bg.ac.rs/handle/123456789/4686