Structure-based drug design and QSAR analysis of candidate drugs for the treatment of cancer

In rational drug design known chemical interactions related to the target disease are exploited to discover novel drugs. By identifying the important reaction pathway and the key enzyme related to a specific disease is the first step in structure-based drug design, then; the active site of the enzyme is analyzed and molecules are designed to competitively bind to that active site.In this study, structure-based rational drug design approach is employed to discover novel inhibitors for two different target proteins. The first target protein is Cytochrome P450 C17, the key enzyme in androgen synthesis and, the second target protein is XPF, a key member of the DNA excision repair system. In designing an inhibitor targeting Cytochrome P450 C17, we aim to prevent the progression of the prostate cancer, and targeting the XPF-ERCC1 pair we aim to design chemotherapeutic agent ?aids? that prevent DNA repair and resistance development in cancerous cells against the chemotherapeutic agents, where as a result we were able to identify several promising candidate drugs.Finally, a novel QSAR approach to predict the activity level of the inhibitors is introduced, since a priori analysis of the activity of inhibitors on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests to save from time and resources. The calculations utilizing the approach presented in this thesis resulted in better accuracies in classifying the activity of candidate drugs among other data mining tools presented in the literature.