Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies
Autor: | Stefanie Hagenow, Tamara R. Todorović, Aleksandar Višnjevac, Aleksandar Lolić, José M. Padrón, Holger Stark, Ivana S. Djordjević, Alfonso T. García-Sosa, Sonja Grubišić, Nenad Filipovic, Hana Elshaflu, Milan Nikolić |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Antioxidant In silico medicine.medical_treatment Hydrazone 01 natural sciences Anticancer activity Docking lcsh:Chemistry 03 medical and health sciences medicine IC50 selenazoles ADME Original Research chemistry.chemical_classification 010405 organic chemistry Chemistry selenazoles MAO B Anticancer activity Docking Antioxidant agents In vitro toxicology General Chemistry 0104 chemical sciences 3. Good health 030104 developmental biology lcsh:QD1-999 Biochemistry Docking (molecular) Antioxidant agents Monoamine oxidase B MAO B |
Zdroj: | Frontiers in Chemistry FRONTIERS IN CHEMISTRY Frontiers in Chemistry, Vol 6 (2018) |
ISSN: | 2296-2646 |
DOI: | 10.3389/fchem.2018.00247 |
Popis: | The novel approach in the treatment of complex multifactorial diseases, such as neurodegenerative disorders and cancer, requires a development of efficient multi-targeting oriented drugs. Since oxidative stress significantly contributes to the pathogenesis of cancer and neurodegenerative disorders, potential drug candidates should possess good antioxidant properties Due to promising biological activities shown for structurally related (1,3-thiazol-2-yl)hydrazones, a focused library of 12 structurally related benzylidene-based (1,3-selenazol-2-yl)hydrazones was designed as potential multi-targeting compounds. Monoamine oxidases (MAO) A/B inhibition properties of this class of compounds have been investigated. Surprisingly, the p-nitrophenyl-substituted (1,3-selenazol-2-yl)hydrazone 4 showed MAO B inhibition in a nanomolar concentration range (IC50 = 73 nM). Excellent antioxidant properties were confirmed in a number of different in vitro assays. Antiproliferative activity screening on a panel of six human solid tumor cell lines showed that potencies of some of the investigated compounds was comparable or even better than that of the positive control 5-fluorouracil. In-silico calculations of ADME properties pointed to promising good pharmacokinetic profiles of investigated compounds. Docking studies suggest that some compounds, compared to positive controls, have the ability to strongly interact with targets relevant to cancer such as 5'-nucleotidase, and to neurodegenerative diseases such as the small conductance calcium-activated potassium channel protein 1, in addition to confirmation of inhibitory binding at MAO B. Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3254] |
Databáze: | OpenAIRE |
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