Design and Synthesis of Heterocycle-based Novel Hybrid Compounds as possible Antimalarial Agents

Abstract

Malaria afflicts more than 3 million people annually, and this debilitating and deadly infectious disease results into a heavy toll on susceptible population around the globe. The present chemotherapy which includes individual drugs and combinations was designed and developed to target the pathogenic blood stages in humans and to address the constant threat of drug resistance. However the use of artemisinin-based combination therapy which still now was considered safe and effective is under threat due to depleting efficacy of artemisinin in endemic areas. Hence the efforts to find effective, safe and low cost drugs for malaria have to be given priority. This exploratory activity is an effort in this direction. The presentation of various chapters are as follows- The first chapter contains a review of the literature highlighting the recent developments in the hybrid antimalarials based on amino quinoline pharmacophore. The basis for the design and selection of the prototype molecules comes into view in the second chapter. Synthesis as well as antimalarial evaluation of pyrrolidinoaminoalkane derivatives of quinoline and some new quinolinomethanols have been discussed in the third chapter. Applications of the 1-formyl-9H-β-carboline for the synthesis of fused β-carbolines which may be considered as analogues of naturally occurring alkaloids via aza-Diels-Alder, multicomponent, ring closing metathesis, Pomeranz-Fritsch and Friedel Craft reactions have been described in the fourth chapter. The results related to the biological screening of these fused β-carbolines are presented at the end of the chapter. The list of publications originating from this endeavour is included at the end. All the chapters have separate bibliography and compound numbering in Arabic.