Conformational Properties of New Thiosemicarbazone and Thiocarbohydrazone Derivatives and Their Possible Targets

Abstract

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.

Exploration of Thiourea-Based Scaffolds for the Construction of Bacterial Ureases Inhibitors

“…Although a mixture of isomers was observed, stereoisomers with the double bonds in the E configuration were the most energy-favorable (Scheme 1). 43 Thiocarbohydrazones 27−31 were obtained by reacting aldehydes 1 and 2 or chalcones 9−11 with thiocarbohydrazide in a mixture of warm ethanol/water using catalytic amounts of acetic acid or 6N HCl. The same trend concerning the double bonds was again observed: derivatives 27−28 were exclusively in the E configuration, while in derivatives 29−31, a mixture of conformers was observed in 1 H and 13 C NMR, with E/E being predominant (Scheme 1).…”

“…The same trend concerning the double bonds was again observed: derivatives 27−28 were exclusively in the E configuration, while in derivatives 29−31, a mixture of conformers was observed in 1 H and 13 C NMR, with E/E being predominant (Scheme 1). 43 Chalcones' constrained cyclized derivatives 32−41 were obtained by following the synthetic routes outlined in Schemes 2 and 3. Chalcones 9−14 reacted with thiosemicarbazide in basic conditions under ultrasonication to give 1H-pyrazole-1carbothioamides 32−36 in medium yield.…”

“…1 (29). 43 Following the general method D for chalcones, using chalcone (9), compound 29 was obtained as a beige solid in 55% yield. R f = 0.87 (1-BuOH/ AcOH/H 2 O 4:1:1).…”

Derivatives Incorporating Acridine, Pyrrole, and Thiazolidine Rings as Promising Antitumor Agents

“…The spiro derivatives 6a – e feature a C=S thiocarbonyl group and two NH labile amide protons, which introduce a propensity for a range of intramolecular transformations in a solution [ 24 , 25 ]. These transformations lead to distinct chemical environments for specific proton and carbon atoms, resulting in variations in chemical shifts for the same proton and carbon nucleus, thus manifesting as signal doubling.…”

Exploring Novel Pyridine Carboxamide Derivatives as Urease Inhibitors: Synthesis, Molecular Docking, Kinetic Studies and ADME Profile

“…The ethanolic solution of semicarbazide and thiosemicarbazide was added to a round bottom flask sequentially and stirred at room temperature, adding different substituted pyridine carboxaldehyde and an aqueous solution of sodium acetate in a 1:1:1 ratio. The reaction product was precipitated out within 30 to 60 min in the purified form with a good-to-excellent yield [ 44 ]. The characterization data can be found in the Supplementary Materials .…”