A Review of Modifications of Quinoline Antimalarials: Mefloquine and (hydroxy)Chloroquine

Late-stage modification of drug molecules is a fast method to introduce diversity into the already biologically active scaffold. A notable number of analogs of mefloquine, chloroquine, and hydroxychloroquine have been synthesized, starting from the readily available active pharmaceutical ingredient (API). In the current review, all the modifications sites and reactivity types are summarized and provide insight into the chemistry of these molecules. The approaches include the introduction of simple groups and functionalities. Coupling to other drugs, polymers, or carriers afforded hybrid compounds or conjugates with either easily hydrolyzable or more chemically inert bonds. The utility of some of the compounds was tested in antiprotozoal, antibacterial, and antiproliferative assays, as well as in enantiodifferentiation experiments.

Automated summary

Late-stage modification of drug molecules is a fast method to increase diversity in already biologically active scaffolds. This review summarizes the modification sites and reactivity types of analogs of mefloquine, chloroquine, and hydroxychloroquine synthesized from readily available active pharmaceutical ingredients (API). The introduction of simple groups and functionalities, as well as coupling with other drugs, polymers, or carriers, resulted in hybrid compounds or conjugates with easily hydrolyzable or more chemically inert bonds. Some of these compounds were tested in antiprotozoal, antibacterial, and antiproliferative assays, as well as enantiodifferentiation experiments.