ABSTRACT
CONTEXT: In this study, the molecular structure of the mexiletine molecule was investigated. Since the Mexiletine molecule is a drug active ingredient, its molecular structure and spectroscopic properties are important. The effects of intramolecular hydrogen bonding on Nuclear Magnetic Resonance Parameters (NMR), Electron Paramagnetic Resonance (EPR) parameters and molecular docking studies were examined in the mexiletine molecule. The effects of intramolecular hydrogen bonding on EPR parameters and molecular docking studies are the most important steps for this study. METHOD: Conformational space scanning required for molecular structure calculations was carried out with the Molecular Mechanic Force Field method. DFT method with 6-311 + + G(d,p) basis set level was used to obtain the most stable structure among the conformations. NMR parameters (1H and 13C chemical shift values) were also performed using the same basis set as the DFT method. The radicals created to calculate the Electron Paramagnetic Resonance parameters were modeled using the DFT/B3LYP/6-311 + + G(d,p) method basis set level. Molecular Docking studies were carried out with the Autodock vina program.
ABSTRACT
In this study, 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) and its novel N(4) substituted derivatives were synthesized and characterized by different techniques. The optical band gap of the compounds and the energy of HOMO were experimentally examined by UV-vis spectra and cyclic voltammetry measurements, respectively. Furthermore, the conformational spaces of the compounds were scanned with molecular mechanics method. The geometry optimization, HOMO and LUMO energies, the energy gap of the HOMO-LUMO, dipole moment of the compounds were theoretically calculated by the density functional theory B3LYP/6-311++G(d,p) level. The minimal electronic excitation energy and maximum wavelength calculations of the compounds were also performed by TD-DFT//B3LYP/6-311++G(d,p) level of theory. Theoretically calculated values were compared with the related experimental values. The combined results exhibit that all compounds have good electron-donor properties which affect anti-proliferative activity. The cytotoxic effects of the compounds were also evaluated against HeLa (cervical carcinoma), MCF-7 (breast carcinoma) and PC-3 (prostatic carcinoma) cell lines using the standard MTT assay. All tested compounds showed antiproliferative effect having IC50 values in different range. In comparison with that of HMAT, it was obtained that while ethyl group on 4(N)-substituted position decreased in potent anti-proliferative effect, the phenyl group on the position increased in anti-proliferative effect for the tested cancer cell line. Considering the molecular energy parameters, the cytotoxicity activities of the compounds were discussed.
