Seite - (000339) - in Biomedical Chemistry: Current Trends and Developments

ongoing as well as the development of novel endoperoxide containing compounds which have proven effective as anti-malarial agents in pre- clinical studies (Lanteri, 2014; Oliveira, 2014). 3.4.4.4 Repurposed Drugs For the treatment of malaria and many other tropical diseases, limitations in funding have led to discoveries in the area of repurposing of drugs commonly used for other indications. Broad spectrum antibiotics have proven highly successful in the treatment of malaria. Doxycycline, a synthetic tetracycline, was shown to have partial prophylactic efficacy against malaria in the 1970’s (Andrews, 2014). In fact, despite its own set of tolerance issues, doxycycline is now the prophylactic drug of choice for the US Army due to more serious concerns with mefloquine (Kime, 2012). It is also effective for use in treatment when partnered with a fast acting anti-malarial like quinine or quinidine (Tan & Centers for Disease Control and Prevention, 2011). Other antibiotics including clindamycin and sulfonamide antibiotics like sulphadiazine and sulphadoxine have also proven effective in the treatment of malaria (Andrews, 2014). Many of these target folate synthesis, which is a common pathway for other classical anti-malarials. Antifolate drugs block the synthesis of tetrahydrofolate, which in turn shuts down nucleic acid synthesis (Shanks, 2006). Among these is dapsone. Dapsone, a sulfone, was first used to treat leprosy but was introduced by GSK as Lapdap (dapsone/chloroproguanil) in the late 1990s. This drug was removed from the market in 2008 due to hemolytic anemia similar to that of the 8-aminoquinolines. Exploration of this strategy still continues with significant effort. Several examples can be found in the literature with protease inhibitors, antibiotics, and quinolones found to act against various targets in the parasite (Rosenthal, 2003). With pre-existing and well established safety profiles, re-purposing of old drugs is an attractive strategy if for no other reason than bypassing several regulatory hurdles and saving money in development. Another potential benefit for the developing world is often the cost of these drugs once marketed. Doxycycline, for example, is pennies per dose compared to Malarone (atovaquone/proguanil) and