Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives
The structure assignment and conformational analysis of the thiosemicarbazones, <b>DKI21</b> and <b>DKI24</b>, were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-ROESY, 2D-HSQC, and 2D-HMBC) and quantum...
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MDPI AG
2022-07-01
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| author | Nikitas Georgiou Antigoni Cheilari Danai Karta Eleni Chontzopoulou Janez Plavec Demeter Tzeli Stamatia Vassiliou Thomas Mavromoustakos |
| author_facet | Nikitas Georgiou Antigoni Cheilari Danai Karta Eleni Chontzopoulou Janez Plavec Demeter Tzeli Stamatia Vassiliou Thomas Mavromoustakos |
| author_sort | Nikitas Georgiou |
| collection | DOAJ |
| description | The structure assignment and conformational analysis of the thiosemicarbazones, <b>DKI21</b> and <b>DKI24</b>, were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-ROESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations, using Functional Density Theory (DFT). In addition, utilizing a combination of 2D-NOESY and 2D-ROESY spectra an <i>exo</i> structure was established for both of the analogs. This experimental results were confirmed by theoretical mechanistic studies, as the lowest minima conformations derived through DFT calculations were compatible with the spatial correlations observed in the 2D-NOESY and 2D-ROESY spectra. Finally, molecular binding experiments were performed to detect the potential targets for <b>DKI21</b> and <b>DKI24</b>, derived from SwissAdme. <i>In silico</i> molecular binding experiments showed favorable binding energy values for the most of the enzymes studied. The ADMET calculations, using the preADMET and pKCSm software, showed that the two molecules appear as possible drug leads. |
| first_indexed | 2024-03-09T13:18:02Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T13:18:02Z |
| publishDate | 2022-07-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-fef110b662d04d32bd1538cb9bff566a2023-11-30T21:34:09ZengMDPI AGMolecules1420-30492022-07-012714454810.3390/molecules27144548Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone DerivativesNikitas Georgiou0Antigoni Cheilari1Danai Karta2Eleni Chontzopoulou3Janez Plavec4Demeter Tzeli5Stamatia Vassiliou6Thomas Mavromoustakos7Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceDepartment of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceSlovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, SloveniaLaboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceThe structure assignment and conformational analysis of the thiosemicarbazones, <b>DKI21</b> and <b>DKI24</b>, were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-ROESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations, using Functional Density Theory (DFT). In addition, utilizing a combination of 2D-NOESY and 2D-ROESY spectra an <i>exo</i> structure was established for both of the analogs. This experimental results were confirmed by theoretical mechanistic studies, as the lowest minima conformations derived through DFT calculations were compatible with the spatial correlations observed in the 2D-NOESY and 2D-ROESY spectra. Finally, molecular binding experiments were performed to detect the potential targets for <b>DKI21</b> and <b>DKI24</b>, derived from SwissAdme. <i>In silico</i> molecular binding experiments showed favorable binding energy values for the most of the enzymes studied. The ADMET calculations, using the preADMET and pKCSm software, showed that the two molecules appear as possible drug leads.https://www.mdpi.com/1420-3049/27/14/4548thiosemicarbazonesNMR spectroscopyquantum mechanicsmolecular bindingDFT |
| spellingShingle | Nikitas Georgiou Antigoni Cheilari Danai Karta Eleni Chontzopoulou Janez Plavec Demeter Tzeli Stamatia Vassiliou Thomas Mavromoustakos Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives Molecules thiosemicarbazones NMR spectroscopy quantum mechanics molecular binding DFT |
| title | Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives |
| title_full | Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives |
| title_fullStr | Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives |
| title_full_unstemmed | Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives |
| title_short | Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives |
| title_sort | conformational properties and putative bioactive targets for novel thiosemicarbazone derivatives |
| topic | thiosemicarbazones NMR spectroscopy quantum mechanics molecular binding DFT |
| url | https://www.mdpi.com/1420-3049/27/14/4548 |
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