Sharif Digital Repository

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. The neuropathology and treatment of AD is not precisely determined yet, but according to the pathological studies, AD is associated with presence of toxic soluble oligomers and insoluble senile plaques formed by amyloidosis of Amyloid Beta (Aβ) in neocortical region of brain. An attractive therapeutic approach to treat AD is to identify small ligands that are capable of binding to critical residues in order to inhibit or reverse Aβ amyloidosis process as source of neurotoxicity. In this area, therapeutic efforts designed various organic agents and most of them focused on the N-terminal sequence of Aβ. The aim of... 

Formation of C-C and C-hetero atom bonds in coupling reactions is among the most important organic chemistry reactions, which is useful for achieving the complex molecules from simple ones. The goal of this thesis, was using the organometallic and also metal free methods in coupling reactions and getting the advantage of them in the synthesis of novel hit compounds. In this way, some novel reactions were designed and some novel catalysts were synthesised and identified. Finally, computational quantum chemistry and computational drug design were used as powerful tools for supporting the reaction mechanism, electronic and structural studies and pharmacological evaluation. C-X bond activation... 

Metal-organic frameworks (MOFs) are a new class of biocompatible nanomaterials with high specific surface area, which provide the possibility of loading various therapeutic agents. Considering the few studies on the use of MOFs in melanoma cancer treatment, the main goal of this research is to investigate the loading and controlling the release of dacarbazine (DTIC) and also the interaction of DTIC and MOF structure in aqueous environments. Based on this, this study was done in three main parts. In the first part, several types of well-known and often used structures in the drug delivery field, including ZIF-8 (based on zinc), MIL-101-NH2(Fe), and MIL-100(Fe) (both based on iron), were... 

SHP2 has been reported as a critical non-receptor phosphatase enzyme that plays crucial roles in numerous disorders like cancer. The previous studies on this enzyme showed that inhibiting the action of the enzyme comes as a way of controlling enzyme activity. SHP099 was discovered as an Allosteric inhibitor of the enzyme with the most inhibitory effect among all of the studied compounds. In this study we aimed to design novel dipeptide-and sugar-based inhibitors for the allosteric binding site of this enzyme with in-silico studies including docking, molecular dynamic simulation, and free binding energy analysis. Our novel designed drugs possess enough binding properties, low toxicity, and... 

Protein activities are modulated by Kinases through phosphate group transfers, regulating cellular functions. Mutations in kinases are related to cancer initiation, progression, and recurrence. Kinase inhibitors such as Crizotinib have demonstrated efficacy against specific cancers, but limitations and adverse effects necessitate the invention and discovery of novel and potent inhibitors. This study employs Computer-Aided Drug Design techniques to develop natural-based structures targeting the ROS1 Kinase Domain. Molecular fingerprints, Molecular Dynamics Simulations, Docking, and Quantum Calculations are utilized for virtual screening and structure evaluations. A compound library is...