الفهرس 
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Abstract
Introduction includes a literature survey on the computer-assisted
approaches to identify new inhibitors via pharmacophore, molecular and
dynamic modeling, quantum mechanics, docking, structural interaction
fingerprints, and statistical learning methods that have been used to identify
new inhibitors. Also, it includes a literature survey on phenothiazines that have boosted the structure-based design of novel compounds and the molecular
modeling of phenothiazines and application of other computer-aided drug
design techniques
CHAPTER II: (Computational Methods)
This chapter includes the use of computational chemistry and overview
on quantum chemical methods, which include semiempirical, Ab Initio and
DFT calculations, and detailed description of the procedures that was used throughout this work. The resulting optimized structures are optimized using
density functional theory (DFT) with the B3LYP and 6-31 G+(d) basis set.
All calculations are performed with the Gaussian 03 software package.
The optimized structures of the molecules are visualized with Chemcraft
program. Molecular frontier orbitals HOMO and LUMO and molecular
electrostatic potential (MEP) of all optimized structures are visualized using GaussView 5.0. The molecular docking simulation is performed using
AutoDock 4.2. Quantitative Structure Activity Relationship (QSAR) is carried
out using the molecular modelling software material studio version 4.3
Accelrys software company.
CHAPTER III: (Results and Discussion)
In this chapter, we analysed and discussed the results of the data obtained from computational studies. This chapter is divided into three main parts:
PART 1: The effect of quantum chemical parameters On the biological activity of trypanothione reductase inhibitors
In this part, the quantum chemical calculations were performed to investigate the effect of electronic and structural parameters on the efficiency of the
studied drugs 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. This study displays 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
This part explains the binding of phenothiazines to the target enzyme. The
docking studies showed that all the tested compounds would bind to the active site of the enzyme, which could be probably due to the presence of lipophilic groups. It was found from the calculations that electrostatic 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.