Mefloquine derivatives : synthesis, mechanisms of action, antimicrobial activities

Malaria is a serious public health problem. More than 100 tropical and sub-tropical countries are endemic for malaria. Pregnant women and children are the most sensitive to this disease and more than 750 000 people die of malaria each year. Among the five species of Plasmodium, P. falciparum is the parasite responsible for the most serious form of the disease and it has developed varying degrees of resistance to many classes of antimalarial drugs; consequently the development of new drugs to treat malaria is in full rise. Mefloquine was proposed, for a long time, as the drug of choice for chloroquineresistant malaria. Emergence of resistance to mefloquine and its associated severe side effects have limited the use of this drug. Nowadays, there is no effective alternative, especially, in the zone of multi-drug resistance. Since a few years, the mechanisms of resistance to antimalarial drugs, the mechanism of action of the mefloquine and the origin of the side effects begin to be understood. On these bases, several approaches are considered to enhance the design of the mefloquine including its synthesis as a pure enantiomer or even the modulation of the mefloquine core as a pure enantiomer.