Conformational Properties of New Thiosemicarbazone and Thiocarbohydrazone Derivatives and Their Possible Targets
Nikitas Georgiou,
Aikaterini Katsogiannou,
Dimitrios Skourtis,
Hermis Iatrou,
Demeter Tzeli,
Stamatia Vassiliou,
Uroš Javornik,
Janez Plavec,
Thomas Mavromoustakos
Affiliations
Nikitas Georgiou
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Aikaterini Katsogiannou
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Dimitrios Skourtis
Laboratory of Polymer Chemistry, Department of Chemistry, National and Kapodistrian Nikitas Georgiou University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Hermis Iatrou
Laboratory of Polymer Chemistry, Department of Chemistry, National and Kapodistrian Nikitas Georgiou University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Demeter Tzeli
Laboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Stamatia Vassiliou
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
Uroš Javornik
Slovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, Slovenia
Janez Plavec
Slovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, Slovenia
Thomas Mavromoustakos
Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece
The structure assignment and conformational analysis of thiosemicarbazone KKI15 and thiocarbohydrazone KKI18 were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations using Functional Density Theory (DFT). After the structure identification of the compounds, various conformations of the two compounds were calculated using DFT. The two molecules showed the most energy-favorable values when their two double bonds adopted the E configuration. These configurations were compatible with the spatial correlations observed in the 2D-NOESY spectrum. In addition, due to the various isomers that occurred, the energy of the transition states from one isomer to another was calculated. Finally, molecular binding experiments were performed to detect potential targets for KKI15 and KKI18 derived from SwissAdme. In silico molecular binding experiments showed favorable binding energy values for all four enzymes studied. The strongest binding energy was observed in the enzyme butyrylcholinesterase. ADMET calculations using the preADMET and pKCSm software showed that the two molecules appear as possible drug leads.
