Molecular modeling studies of sulfur containing shikonin oxime derivatives and design of new derivatives

Derivatives of shikonin are in the group of important compounds in terms of their anti-cancer properties and their use as drugs. Nowadays, breast cancer treatments have many side effects, but they have a limited variety of drugs. In this thesis, it is aimed to design new molecules that can be a drug precursor in breast cancer by derivatizing sulphur-containing shikonin oxime derivatives. Firstly, models explaining quantitative structure-effect-activity relationships (QSAR) were created by applying statistical algorithms to the molecular descriptor properties, calculated by quantum chemical methods, for shikonin oxime derivatives, whose experimental biological activities are known in the literature. The relationship between the the activities we calculated with the models and their experimental activities are explained. Then, virtual molecules that could fit the QSAR model and which we think could be drug precursors in the treatment of breast cancer were designed. Molecules with known experimental biological activities and designed molecules have been performed to explain their binding to the estrogen receptor (ER) (PDB ID: 26OK), which is known to bind very well to many drugs used in the treatment of breast cancer. In addition, to test the docking studies, a group of drugs used in the treatment of breast cancer were selected and their binding to the same receptor was performed. The studies continued by calculating the absorption, distribution, metabolization and excretion (ADME) properties within the organism, such as bioavailability, physicochemical properties, pharmacokinetics, water solubility, lipophilicity, drug similarity, of all the molecules studied. Finally, the results of QSAR docking and ADME studies, the synthesibility of the molecule and the availability of the starting material and whether it is economical or not, were examined in order to bring it to the fields of chemistry, medicine, and pharmacy as a new drug derivative in breast cancer, and the benzyl derivative, which is the most suitable and high biological activity virtual molecule for the derived model, was synthesized. Thus, ligand-protein docking has been determined in drug design and and a contribution to the literature was made in elucidating the biochemical process.