Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies
2018
Authors
Elshaflu, HanaTodorović, Tamara R.
Nikolić, Milan
Lolić, Aleksandar
Visnjevac, Aleksandar
Hagenow, Stefanie
Padron, Jose M.
Garcia-Sosa, Alfonso T.
Djordjević, Ivana S.
Grubisić, Sonja
Stark, Holger
Filipović, Nenad
Article (Published version)
Metadata
Show full item recordAbstract
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.
Keywords:
selenazoles / MAO B / Anticancer activity / Docking / Antioxidant agentsSource:
Frontiers in Chemistry, 2018, 6Publisher:
- Frontiers Media Sa, Lausanne
Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
- Estonian Ministry for Education and Research [IUT34-14]
- German Research Foundation (DFG)German Research Foundation (DFG) [INST 208/664-1 FUGG]
- COST ActionEuropean Cooperation in Science and Technology (COST) [CA15135]
DOI: 10.3389/fchem.2018.00247
ISSN: 2296-2646
PubMed: 30018949
WoS: 000437129200001
Scopus: 2-s2.0-85053084992
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Institution/Community
Poljoprivredni fakultetTY - JOUR AU - Elshaflu, Hana AU - Todorović, Tamara R. AU - Nikolić, Milan AU - Lolić, Aleksandar AU - Visnjevac, Aleksandar AU - Hagenow, Stefanie AU - Padron, Jose M. AU - Garcia-Sosa, Alfonso T. AU - Djordjević, Ivana S. AU - Grubisić, Sonja AU - Stark, Holger AU - Filipović, Nenad PY - 2018 UR - http://aspace.agrif.bg.ac.rs/handle/123456789/4773 AB - 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. PB - Frontiers Media Sa, Lausanne T2 - Frontiers in Chemistry T1 - Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies VL - 6 DO - 10.3389/fchem.2018.00247 ER -
@article{ author = "Elshaflu, Hana and Todorović, Tamara R. and Nikolić, Milan and Lolić, Aleksandar and Visnjevac, Aleksandar and Hagenow, Stefanie and Padron, Jose M. and Garcia-Sosa, Alfonso T. and Djordjević, Ivana S. and Grubisić, Sonja and Stark, Holger and Filipović, Nenad", year = "2018", abstract = "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.", publisher = "Frontiers Media Sa, Lausanne", journal = "Frontiers in Chemistry", title = "Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies", volume = "6", doi = "10.3389/fchem.2018.00247" }
Elshaflu, H., Todorović, T. R., Nikolić, M., Lolić, A., Visnjevac, A., Hagenow, S., Padron, J. M., Garcia-Sosa, A. T., Djordjević, I. S., Grubisić, S., Stark, H.,& Filipović, N.. (2018). Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies. in Frontiers in Chemistry Frontiers Media Sa, Lausanne., 6. https://doi.org/10.3389/fchem.2018.00247
Elshaflu H, Todorović TR, Nikolić M, Lolić A, Visnjevac A, Hagenow S, Padron JM, Garcia-Sosa AT, Djordjević IS, Grubisić S, Stark H, Filipović N. Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies. in Frontiers in Chemistry. 2018;6. doi:10.3389/fchem.2018.00247 .
Elshaflu, Hana, Todorović, Tamara R., Nikolić, Milan, Lolić, Aleksandar, Visnjevac, Aleksandar, Hagenow, Stefanie, Padron, Jose M., Garcia-Sosa, Alfonso T., Djordjević, Ivana S., Grubisić, Sonja, Stark, Holger, Filipović, Nenad, "Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies" in Frontiers in Chemistry, 6 (2018), https://doi.org/10.3389/fchem.2018.00247 . .