TY  - JOUR
AU  - Dimic, Dusan S.
AU  - Kaluderović, Goran N.
AU  - Avdović, Edina H.
AU  - Milenković, Dejan
AU  - Živanović, Marko N.
AU  - Potocnak, Ivan
AU  - Samolova, Erika
AU  - Dimitrijević, Milena
AU  - Saso, Luciano
AU  - Marković, Zoran S.
AU  - Dimitrić-Marković, Jasmina
PY  - 2022
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1534
AB  - In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives
IS  - 2
VL  - 23
DO  - 10.3390/ijms23021001
ER  - 

@article{
author = "Dimic, Dusan S. and Kaluderović, Goran N. and Avdović, Edina H. and Milenković, Dejan and Živanović, Marko N. and Potocnak, Ivan and Samolova, Erika and Dimitrijević, Milena and Saso, Luciano and Marković, Zoran S. and Dimitrić-Marković, Jasmina",
year = "2022",
abstract = "In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives",
number = "2",
volume = "23",
doi = "10.3390/ijms23021001"
}

Dimic, D. S., Kaluderović, G. N., Avdović, E. H., Milenković, D., Živanović, M. N., Potocnak, I., Samolova, E., Dimitrijević, M., Saso, L., Marković, Z. S.,& Dimitrić-Marković, J.. (2022). Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives. in International Journal of Molecular Sciences
MDPI, Basel., 23(2).
https://doi.org/10.3390/ijms23021001

Dimic DS, Kaluderović GN, Avdović EH, Milenković D, Živanović MN, Potocnak I, Samolova E, Dimitrijević M, Saso L, Marković ZS, Dimitrić-Marković J. Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives. in International Journal of Molecular Sciences. 2022;23(2).
doi:10.3390/ijms23021001 .

Dimic, Dusan S., Kaluderović, Goran N., Avdović, Edina H., Milenković, Dejan, Živanović, Marko N., Potocnak, Ivan, Samolova, Erika, Dimitrijević, Milena, Saso, Luciano, Marković, Zoran S., Dimitrić-Marković, Jasmina, "Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives" in International Journal of Molecular Sciences, 23, no. 2 (2022),
https://doi.org/10.3390/ijms23021001 . .

TY  - JOUR
AU  - Milanović, Ziko
AU  - Dimic, Dusan
AU  - Žižić, Milan
AU  - Milenković, Dejan
AU  - Marković, Zoran
AU  - Avdović, Edina
PY  - 2021
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1504
AB  - Coumarin derivatives have proven beneficial biological activities, but the mechanism of their radical scavenging potency is not fully understood. In this study, the antiradical capacity of two newly synthesized 4,7-dihydroxycoumarin derivatives: (E)-3-(1-((3-hydroxy-4-methoxyphenyl)amino)-ethylidene)-2,4-dioxochroman-7-yl acetate (A-3OH) and (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A-4OH) towards HO center dot were examined by Electron Paramagnetic Resonance (EPR) Spectroscopy and Density Functional Theory (DFT). The compounds were fully characterized by the elemental microanalysis, IR, and NMR spectroscopies. The effect of pH on the acid-base equilibria is separately discussed and the predominant species at the physiological pH were determined. Several common mechanisms (Hydrogen Atom Transfer (HAT), Single-Electron Transfer followed by Proton Transfer (SET-PT), Sequential Proton Loss followed by Electron Transfer (SPLET), Radical Adduct Formation (RAF), and Intramolecular Hydrogen Atom Abstraction (iHAA)) of radical scavenging were investigated based on thermodynamic and kinetic parameters. EPR results indicated that both compounds significantly reduce the amount of present HO center dot. The results of the kinetic DFT study demonstrated that both compounds predominantly exhibit antiradical capacity through HAT and SPLET mechanisms. The estimated overall rate constants (k(overall)) proved that A-4OH shows better antioxidant capacity than A-3OH which is well-correlated with the results obtained by EPR measurement.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study
IS  - 24
VL  - 22
DO  - 10.3390/ijms222413273
ER  - 

@article{
author = "Milanović, Ziko and Dimic, Dusan and Žižić, Milan and Milenković, Dejan and Marković, Zoran and Avdović, Edina",
year = "2021",
abstract = "Coumarin derivatives have proven beneficial biological activities, but the mechanism of their radical scavenging potency is not fully understood. In this study, the antiradical capacity of two newly synthesized 4,7-dihydroxycoumarin derivatives: (E)-3-(1-((3-hydroxy-4-methoxyphenyl)amino)-ethylidene)-2,4-dioxochroman-7-yl acetate (A-3OH) and (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A-4OH) towards HO center dot were examined by Electron Paramagnetic Resonance (EPR) Spectroscopy and Density Functional Theory (DFT). The compounds were fully characterized by the elemental microanalysis, IR, and NMR spectroscopies. The effect of pH on the acid-base equilibria is separately discussed and the predominant species at the physiological pH were determined. Several common mechanisms (Hydrogen Atom Transfer (HAT), Single-Electron Transfer followed by Proton Transfer (SET-PT), Sequential Proton Loss followed by Electron Transfer (SPLET), Radical Adduct Formation (RAF), and Intramolecular Hydrogen Atom Abstraction (iHAA)) of radical scavenging were investigated based on thermodynamic and kinetic parameters. EPR results indicated that both compounds significantly reduce the amount of present HO center dot. The results of the kinetic DFT study demonstrated that both compounds predominantly exhibit antiradical capacity through HAT and SPLET mechanisms. The estimated overall rate constants (k(overall)) proved that A-4OH shows better antioxidant capacity than A-3OH which is well-correlated with the results obtained by EPR measurement.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study",
number = "24",
volume = "22",
doi = "10.3390/ijms222413273"
}

Milanović, Z., Dimic, D., Žižić, M., Milenković, D., Marković, Z.,& Avdović, E.. (2021). Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study. in International Journal of Molecular Sciences
MDPI, Basel., 22(24).
https://doi.org/10.3390/ijms222413273

Milanović Z, Dimic D, Žižić M, Milenković D, Marković Z, Avdović E. Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study. in International Journal of Molecular Sciences. 2021;22(24).
doi:10.3390/ijms222413273 .

Milanović, Ziko, Dimic, Dusan, Žižić, Milan, Milenković, Dejan, Marković, Zoran, Avdović, Edina, "Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study" in International Journal of Molecular Sciences, 22, no. 24 (2021),
https://doi.org/10.3390/ijms222413273 . .

TY  - JOUR
AU  - Dimitrić-Marković, Jasmina
AU  - Pejin, Boris
AU  - Milenković, Dejan
AU  - Amic, Dragan
AU  - Begović, Nebojša
AU  - Mojović, Miloš
AU  - Marković, Zoran S.
PY  - 2017
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1103
AB  - Naturally occurring flavonoids, delphinidin, pelargonidin and malvin, were investigated experimentally and theoretically for their ability to scavenge hydroxyl and nitric oxide radicals. Electron spin resonance (ESR) spectroscopy was used to determine antiradical activity of the selected compounds and M05-2X/6-311+G(d,p) level of theory for the calculation of reaction enthalpies related to three possible mechanisms of free radical scavenging activity, namely HAT, SET-PT and SPLET. The results obtained show that the molecules investigated reacted with hydroxyl radical via both HAT and SPLET in the solvents investigated. These results point to HAT as implausible for the reaction with nitric oxide radical in all the solvents investigated. SET-PT also proved to be thermodynamically unfavourable for all three molecules in the solvents considered.
PB  - Elsevier Sci Ltd, Oxford
T2  - Food Chemistry
T1  - Antiradical activity of delphinidin, pelargonidin and malvin towards hydroxyl and nitric oxide radicals: The energy requirements calculations as a prediction of the possible antiradical mechanisms
EP  - 446
SP  - 440
VL  - 218
DO  - 10.1016/j.foodchem.2016.09.106
ER  - 

@article{
author = "Dimitrić-Marković, Jasmina and Pejin, Boris and Milenković, Dejan and Amic, Dragan and Begović, Nebojša and Mojović, Miloš and Marković, Zoran S.",
year = "2017",
abstract = "Naturally occurring flavonoids, delphinidin, pelargonidin and malvin, were investigated experimentally and theoretically for their ability to scavenge hydroxyl and nitric oxide radicals. Electron spin resonance (ESR) spectroscopy was used to determine antiradical activity of the selected compounds and M05-2X/6-311+G(d,p) level of theory for the calculation of reaction enthalpies related to three possible mechanisms of free radical scavenging activity, namely HAT, SET-PT and SPLET. The results obtained show that the molecules investigated reacted with hydroxyl radical via both HAT and SPLET in the solvents investigated. These results point to HAT as implausible for the reaction with nitric oxide radical in all the solvents investigated. SET-PT also proved to be thermodynamically unfavourable for all three molecules in the solvents considered.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Food Chemistry",
title = "Antiradical activity of delphinidin, pelargonidin and malvin towards hydroxyl and nitric oxide radicals: The energy requirements calculations as a prediction of the possible antiradical mechanisms",
pages = "446-440",
volume = "218",
doi = "10.1016/j.foodchem.2016.09.106"
}

Dimitrić-Marković, J., Pejin, B., Milenković, D., Amic, D., Begović, N., Mojović, M.,& Marković, Z. S.. (2017). Antiradical activity of delphinidin, pelargonidin and malvin towards hydroxyl and nitric oxide radicals: The energy requirements calculations as a prediction of the possible antiradical mechanisms. in Food Chemistry
Elsevier Sci Ltd, Oxford., 218, 440-446.
https://doi.org/10.1016/j.foodchem.2016.09.106

Dimitrić-Marković J, Pejin B, Milenković D, Amic D, Begović N, Mojović M, Marković ZS. Antiradical activity of delphinidin, pelargonidin and malvin towards hydroxyl and nitric oxide radicals: The energy requirements calculations as a prediction of the possible antiradical mechanisms. in Food Chemistry. 2017;218:440-446.
doi:10.1016/j.foodchem.2016.09.106 .

Dimitrić-Marković, Jasmina, Pejin, Boris, Milenković, Dejan, Amic, Dragan, Begović, Nebojša, Mojović, Miloš, Marković, Zoran S., "Antiradical activity of delphinidin, pelargonidin and malvin towards hydroxyl and nitric oxide radicals: The energy requirements calculations as a prediction of the possible antiradical mechanisms" in Food Chemistry, 218 (2017):440-446,
https://doi.org/10.1016/j.foodchem.2016.09.106 . .