Synthesis of novel chiral TBBt derivatives with hydroxyl moiety. Studies on inhibition of human protein kinase CK2a and cytotoxicity properties
PBN-AR
Instytucja
Wydział Chemiczny (Politechnika Warszawska)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
European Journal of Medicinal Chemistry
ISSN
0223-5234
EISSN
Wydawca
DOI
URL
Rok publikacji
2014
Numer zeszytu
Strony od-do
364-374
Numer tomu
84
Identyfikator DOI
Liczba arkuszy
0.5
Słowa kluczowe
en
4,5,6,7-Tetrabromo-1H-benzotriazole; Protein kinase CK2; Inhibitors; Molecular docking; Cytotoxicity evaluations; Anti-tumor therapies
Streszczenia
Język
en
Treść
The efficient method for the synthesis of novel 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) derivatives bearing a single stereogenic center has been developed. New compounds with a variety of substituents at the meta- and para-position of the phenyl ring are reported. All of the presented compounds were obtained using classical synthetic methods, such as bromination of benzotriazole, and its subsequent alkylation by monotosylated arylpropane-1,3-diols, which in turn have been synthesized through reduction of the corresponding prochiral b-keto esters, and the selective monotosylation of the primary hydroxyl group. The influence of the new and previously reported N-hydroxyalkyl TBBt derivatives on the activity of human protein kinase CK2a catalytic subunit was examined. The most active were derivatives with N-hydroxyalkyl substituents (IC50 in 0.80e7.35 mM range). A binding mode of (R)-1-(4,5,6,7-tetrabromo-2H-benzotriazol-2-yl)butan-3-ol 7b to hCK2a has been proposed based on in silico docking studies. Additionally, MTT-based cytotoxicity tests demonstrated high activities of novel 1-aryl-3-TBBt-propan-1-ol and 3-TBBt-propan-1,2-diol derivatives against human peripheral blood T lymphoblast (CCRF-CEM), and moderate anti-tumor activities against human breast adenocarcinoma (MCF7) cell lines.
Inne
System-identifier
WUT475149b3e3c8484db4e53b5f244590fc
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