Chapter 2 - Recent progress in the synthesis of antimalarial indoloquinoline natural products and analogues

Abstract

Abstract Clinically used malaria drugs are suffering from increasing drug resistance and with that, the necessity to develop new antimalarial treatments is of great need. Natural products have traditionally been a good source of compounds for the treatment of malaria with the two most well-known drugs being the natural products quinine and artemisinin. These compounds used either alone or in combination with other drugs have provided a good arsenal for combating malaria. Synthetic analogues of the two natural products have also been used with great success in the past. However, increasing drug resistance has made these drugs and combinations of them inactive in some regions of the world. There is therefore a constant need for finding new molecules that can help fight malaria. Natural products are still a rich source of new lead compounds with antimalarial activity as it has been in the past. Over the years, a variety of different compounds have been isolated possessing interesting activity toward malaria. Many of these molecules have inspired synthetic campaigns firstly targeted at preparing the natural products, and secondly to generate analogues of the natural products with the aim to generate compounds with enhanced biological activity. This chapter will focus on the recent progress in the synthesis of the indoloquinoline natural products isocryptolepin, neocryptolepin, and cryptolepine, all possessing antimalarial activity, and synthetic efforts invested into generating more potent analogues of the parent compounds.