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
