X-Ray Crystallographic studies of Some Molecules of Biological and Structural Interest

Abstract

Keeping in mind the ultimate goal as to be able to design and synthesize better ligands as potent drug candidates, medicinal chemist needs new chemical entities (NCEs) with the incorporation of knowledge from other advance growing fields such as X-ray crystallography, computer aided drug design (CADD) and molecular modeling. This thesis focuses the technique of X-ray crystallography used in the field of drug design. This brief review presented here suggests that although crystallography is a relatively old technique, it has yet to reveal many mysteries of the molecular world. The structural knowledge of the small molecules is the most important part of the structure based drug design. The work reported in this thesis attempts to combine the structuralelucidation through X-ray crystallography and the knowledge of binding activities of these structural moieties with target receptors gained from the in-silico methods, towards the drug development. The thesis has been organized under five main chapters: Chapter 1 presents an overview of crystallography as a tool and the application of crystal structure analysis in understanding the noncovalent interactions and subsequent utilization in the drug development. Chapter 2 “Experimental Methodology” deals with the X-ray Crystallographic theory and formulas used for structure determinations and structural analysis of small molecules. Chapter 3 provides an account of the X-ray crystallographic studies on pyrazolo[3,4-d]pyrimidine core based flexible molecules for understanding Arene interactions. Chapter 4 deals with the X-ray crystallographic and in-silico docking studies of selective estrogen receptor modulators. This chapter is divided in two parts. In the first part X-ray structural studies and in-silico docking studies of spiro-oxindole derivatives are discussed. The second part discusses X-ray structural studies and in silico docking studies of coumarin derivatives. Both these derivatives are evaluated in-silico as anti-breast cancer agents