Selenazolyl-hydrazones as Novel Selective MAO Inhibitors With Antiproliferative and Antioxidant Activities: Experimental and In-silico Studies
2018
Authors
Elshaflu, HanaTodorović, Tamara
Nikolić, Milan
Lolić, Aleksandar
Višnjevac, Aleksandar
Hagenow, Stefanie
Padrón, José M.
Garcia-Sosa, Alfonso T.
Đorđević, Ivana S.
Grubišić, Sonja
Stark, Holger
Filipović, Nenad R.
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-MESTD-Basic Research (BR or ON)-172055)
- German Research Foundation (DFG) [INST 208/664-1 FUGG]
- COST Action [CA15135]
- Estonian Ministry for Education and Research [IUT34-14]
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3254
DOI: 10.3389/fchem.2018.00247
ISSN: 2296-2646
PubMed: 30018949
WoS: 000437129200001
Scopus: 2-s2.0-85053084992
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Elshaflu, Hana AU - Todorović, Tamara AU - Nikolić, Milan AU - Lolić, Aleksandar AU - Višnjevac, Aleksandar AU - Hagenow, Stefanie AU - Padrón, José M. AU - Garcia-Sosa, Alfonso T. AU - Đorđević, Ivana S. AU - Grubišić, Sonja AU - Stark, Holger AU - Filipović, Nenad R. PY - 2018 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2172 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 and Nikolić, Milan and Lolić, Aleksandar and Višnjevac, Aleksandar and Hagenow, Stefanie and Padrón, José M. and Garcia-Sosa, Alfonso T. and Đorđević, Ivana S. and Grubišić, Sonja and Stark, Holger and Filipović, Nenad R.", 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., Nikolić, M., Lolić, A., Višnjevac, A., Hagenow, S., Padrón, J. M., Garcia-Sosa, A. T., Đorđević, I. S., Grubišić, S., Stark, H.,& Filipović, N. R.. (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 T, Nikolić M, Lolić A, Višnjevac A, Hagenow S, Padrón JM, Garcia-Sosa AT, Đorđević IS, Grubišić S, Stark H, Filipović NR. 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, Nikolić, Milan, Lolić, Aleksandar, Višnjevac, Aleksandar, Hagenow, Stefanie, Padrón, José M., Garcia-Sosa, Alfonso T., Đorđević, Ivana S., Grubišić, Sonja, Stark, Holger, Filipović, Nenad R., "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 . .