ABSTRACT
This chapter deals with my initial experience with the concept of structure-activity relationship (SAR) and the mechanism of action of drugs that I learned in undergraduate courses. Later, in graduate school, and inspired by the structures of known antimalarial agents, such as Chloroquine and Amodiaquine, I describe how I used sophisticated SAR concepts to design and synthesize novel antimalarial agents during my training. This research was critical during the Vietnam War. Determining the mechanism of action of the newly designed antimalarial agents was fundamental to understand the role of the different side chains of Chloroquine and Amodiaquine—respectively linear and aromatic—in aiding or hindering the intercalation of these agents into DNA. The extent of intercalation was determined by measuring the increase in the melting temperature (Tm) of DNA before and after exposure to the drugs. This chapter also describes novel methods of synthesis of biogenic 4-hydroxytryptamines.
