PTA Ruthenium-aminochloroquinoline complexes: Antimalarials of the future

Abstract: Malaria is a disease that is transmitted by mosquitoes; it has been transmitedaffecting humanity for more than 10.000 years, it affects between 700 000 and 2.7million people per year and it can be deadly, therefore there is a large and increasinginterest in developing a cure against it. Quinine, the first antimalarial, was isolated from the chinchona tree in 1632. Thiscompound was widely used in the form of tonic water, but afterwards, a decrease ofits antimalarial effectivity was observed and in 1910 it was concluded that thissituation was because the parasite that causes malaria had developed a resistanceagainst the quinine. This situation inspired the scientific community to find new options to fight thesickness. In 1934, chloroquine was developed by German scientists and was themost used antimalarial until the 1950's, when parasitic resistance again occurred.Other medicaments like mefloquine and arteminisin have been developed but theresistance problem still exists thus maintaining interest in the development of for newtreatments. The success of the anticancer medicine cisplatin and other metal-based drugs hasincreased interest in inorganic medicinal chemistry. Therefore scientists came to theidea of coupling a known antimalarial with a organometallic species thus creatingorganometallic antimalarial complexes that are not only effective but the parasitedoes not develop resistance against it. Studies of ferroquine, a chloroquinolinederivative coupled with a ferrocene molecule, showed fantastic results and it is inphase IIb of medical trials. Chloroquine derivatives may be coupled with metals like ruthenium, iron, iridium andrhodium, and the first studies showed similar results (increased antimalarial activitywithout the resistance) to those from the ferroquine studies, indicating the greatfuture and potential of these compounds. This chemistry is still on in the developmentphase. This project is involved with the development of organometallic antimalarialcompounds. Specifically ruthenium-chloroquine complexes coupled with a water-soluble phosphine molecule (PTA) were targeted in order to create antimalarialcomplexes with good aqueous solubility, which may be of importance to, theirantimalarial effectivity