الفهرس 
Drugs and the medicinal chemistOnly 14 pages are availabe for public view
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Abstract
The entitled thesis “Molecular Modeling and Quantum Chemical Studies of the Inhibition Efficiency of Some Drugs” comprises three chapters, introduction and literature survey, computational methods and results and discussion. Also, it contains 72 Figures, 58 Tables and 148 references. CHAPTER I: (Introduction and literature Survey). includes a literature survey on hydroxyl ethyl amine (HEA) derivatives that have boosted the structure-based design of novel compounds, the molecular modeling of HEA and application of other computer-aided drug design techniques. Also, it concludes a literature survey on the recently published drugs which have been used to improve the BACE-1 inhibitory activity through a structure-based design. CHAPTER II: (Computational Methods). This chapter discusses the use of computational chemistry and overview on quantum chemical methods used which include ab initio and DFT calculations. Detail description of the procedures was shown throughout this work. The molecular structures of the investigated compounds were optimized using DFT with the B3LYP and 6-31G(d) basis set. All calculations were performed with the Gaussian 03 program package. The optimized structures of the molecules were visualized with GaussView program. Molecular frontier orbitals HOMO, LUMO and molecular electrostatic potential (MEP) of all optimized structures were visualized with Molekel 4.3. Natural bond orbital (NBO) calculations were performed using NBO 3.1 program as implemented in the Gaussian 03 package at the DFT/B3LYP/6-31G(d) level to understand various second-order interactions between the filled orbitals English of one subsystem and the vacant orbitals of another subsystem, which is a measure of the intera-molecular delocalization or conjugation. The individual atomic charges calculated by Mulliken population analysis (MPA) have been used to calculate the Fukui function. The molecular docking simulation was performed using Molegro Virtual Docker (MVD). The Quantitative Structure Activity Relationship (QSAR) was carried out using the molecular modeling software Material Studio version 4.3, Accelrys software company. CHAPTER III: (Results and Discussion). This chapter deals with the results and discussion of the data obtained from theoretical studies. This chapter is divided into two main parts: PART 1. The correlation of quantum chemical parameters with the IC50 of HEA β-secretase inhibitors: In this part, the quantum chemical calculations were performed using DFT /B3LYP at 6-31G (d) basis set to investigate the effect of electronic and structural parameters on the efficiency of the studied compounds and try to predict the mode of interaction of the inhibitor with the enzyme. The quantum chemical calculations showed an agreement between quantum chemical parameters related to the electronic structure of the investigated compounds and their biological activity. Finally, this study displayed a good correlation between the theoretical and experimental data which confirmed that the quantum chemical methods are successful tools for enriching screening experiments aimed at the discovery of novel bioactive compounds. PART 2: Molecular docking analysis: The docking studies showed that all the investigated compounds bind to the active sites of the enzyme probably through the lipophilic groups such as isophthalamide nucleus (S2) moiety and benzene ring in (S1) moiety. It was found from the calculations that the hydrogen bonds and the van der Waals forces are the main features of the interaction. Also, good correlations were found between the data obtained from the docking calculations and the calculated quantum chemical parameters. Quantitative structure-activity relationship (QSAR) showed a mathematical relationship between IC50 of a molecular system and a set of descriptors of molecules based on its geometric and chemical characteristics. Objective feature selection uses the independent variables alone to filter out the non useful descriptors without using the dependent variables. This equation showed a good statistical data and the obtained statistical model has a correlation coefficient, R= 0.88, which supports the reliability and goodness of the model. Finally, the thesis ends with a list of references which were helpful during the study and Arabic summary.