Quantum Chemical Studies on Some Thiosemicarbazone Derivatives as Ribonucleotide Reductase Inhibitor
Mustafa Lawar *
Higher Instiute of Medical Proffessionals, Absalim, Tripoli, Libya and Department of Genetic and Bioengineering, Kastamonu University, Kastamonu, Turkey
Safia Badwe
Department of Statistics, Faculty of Science, Tripoli University, Tripoli, Libya and Modes and Design Engineering System Department, School of Natural and Applied Science, Atilim University, Ankara, Turkey
Ismail Yalçin
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey
Kayhan Bolelli
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey
Hakan Sezgin Sayiner
Department of Infectious Diseases, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey
Fatma Kandemirli
Department of Biomedical Engineering, Faculty of Engineering and Architecture, Kastamonu University, Kastamonu, Turkey
*Author to whom correspondence should be addressed.
Abstract
QSAR analysis of thiosemicarbazone derivatives exposing RNR inhibitory activities [1] was performed for 21 compounds. Among these compounds, 13 of them were reported with inhibitory concentration (IC50) in the l M range. The inhibitory concentration of those compounds was converted into -logIC50 before being correlated with the structural features.
The quantum chemical calculations have been carried out at the B3LYP at Complete Basis set (CBS) level of theory using Gaussian-09 series of program package. The density functional theory (DFT), Becke’s three parameter exchange function along with the Lee–Yang–Parr correlation function (B3LYP) were considered to calculate the quantum chemical descriptors such as HOMO, LUMO, Energy gap, Hardness, Softness, Chemical potential and Dipole moment of the investigated molecules. The variables make a unique statistically significant contribution (p < 0.05). According to their beta values, electronegativity showed the biggest beta coefficient (–13.225). It has been revealed that variable has a unique contribution to a stronger explanation of dependent variables. Beta values for the electrofugality was slightly lower (8.350) , showing least contribution for rest of the elements. Other variables (Energy gap, chemical potential, nucleofugality) measured for this model was statistically significant.
Keywords: Ribonucleotide reductase (RNR), thiosemicarbazones derivatives, RNR inhibitory activities, methoxy group (OCH3)