Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives
2022
Аутори
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
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 c...ancer (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.
Кључне речи:
X-ray crystallography / neurotransmitter / molecular dynamics / molecular docking / DFT / coumarinИзвор:
International Journal of Molecular Sciences, 2022, 23, 2Издавач:
- MDPI, Basel
Финансирање / пројекти:
- Science Fund of the Republic of Serbia [6388843]
- grant VEGAVedecka grantova agentura MSVVaS SR a SAV (VEGA) [1/0148/19]
- Operation program Prague Competitiveness-project [CZ.2.16/3.1.00/24510]
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200378 (Институт за информационе технологије, Крагујевац) (RS-MESTD-inst-2020-200378)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200122 (Универзитет у Крагујевцу, Природно-математички факултет) (RS-MESTD-inst-2020-200122)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200146 (Универзитет у Београду, Факултет за физичку хемију) (RS-MESTD-inst-2020-200146)
DOI: 10.3390/ijms23021001
ISSN: 1422-0067
PubMed: 35055194
WoS: 000749885000001
Scopus: 2-s2.0-85123425882
Институција/група
Institut za multidisciplinarna istraživanjaTY - 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 . .