Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives
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...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/2/1001 |
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| author | Dušan S. Dimić Goran N. Kaluđerović Edina H. Avdović Dejan A. Milenković Marko N. Živanović Ivan Potočňák Erika Samoľová Milena S. Dimitrijević Luciano Saso Zoran S. Marković Jasmina M. Dimitrić Marković |
| author_facet | Dušan S. Dimić Goran N. Kaluđerović Edina H. Avdović Dejan A. Milenković Marko N. Živanović Ivan Potočňák Erika Samoľová Milena S. Dimitrijević Luciano Saso Zoran S. Marković Jasmina M. Dimitrić Marković |
| author_sort | Dušan S. Dimić |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:16:19Z |
| format | Article |
| id | doaj.art-a4178c5fb34b43fd8ab79a1b76ad7807 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:16:19Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a4178c5fb34b43fd8ab79a1b76ad78072023-11-23T14:08:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01232100110.3390/ijms23021001Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter DerivativesDušan S. Dimić0Goran N. Kaluđerović1Edina H. Avdović2Dejan A. Milenković3Marko N. Živanović4Ivan Potočňák5Erika Samoľová6Milena S. Dimitrijević7Luciano Saso8Zoran S. Marković9Jasmina M. Dimitrić Marković10Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, SerbiaDepartment of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, DE-06217 Merseburg, GermanyDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaInstitute of Chemistry, P. J. Šafárik University in Košice, Moyzesova 11, 04154 Košice, SlovakiaInstitute of Physics of the Czech Academy of Sciences, Na Slovance 2, 182 21 Prague 8, Czech RepublicDepartment of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030 Belgrade, SerbiaDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, SerbiaFaculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, SerbiaIn 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.https://www.mdpi.com/1422-0067/23/2/1001coumarinneurotransmittermolecular dockingmolecular dynamicsDFTX-ray crystallography |
| spellingShingle | Dušan S. Dimić Goran N. Kaluđerović Edina H. Avdović Dejan A. Milenković Marko N. Živanović Ivan Potočňák Erika Samoľová Milena S. Dimitrijević Luciano Saso Zoran S. Marković Jasmina M. Dimitrić Marković Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives International Journal of Molecular Sciences coumarin neurotransmitter molecular docking molecular dynamics DFT X-ray crystallography |
| title | Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives |
| title_full | Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives |
| title_fullStr | Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives |
| title_full_unstemmed | Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives |
| title_short | Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives |
| title_sort | synthesis crystallographic quantum chemical antitumor and molecular docking dynamic studies of 4 hydroxycoumarin neurotransmitter derivatives |
| topic | coumarin neurotransmitter molecular docking molecular dynamics DFT X-ray crystallography |
| url | https://www.mdpi.com/1422-0067/23/2/1001 |
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