A diversity-oriented synthesis (DOS) approach for the functionalisation of benzo(g)(iso)quinoline--5,10-dione derivates with potential anti-plasmodial and anti-mycobacterial activity.

According to WHO estimates malaria accounted in 2010 for almost 660,000 deaths, and even more important, 220 million people suffer daily from malaria. The emerging resistance of the malarial blood parasite Plasmodium falciparum to drugs like chloroquine and the artemisinines, especially in the Mekong delta, urges the development of new anti-plasmodial compounds. Likewise, tuberculosis (caused by Mycobacterium tuberculosis) is a worldwide health problem. Several, benzo[g] isoquinoline-5,10-dione derivatives were found active against P. falciparum (chloroquine resistant) and M. tuberculosis, but suffered from strong cytotoxicity. Therefore, a medicinally driven synthetic program is proposed here for the synthesis of a wide variety of benzo[g]isoquinoline-5,10-diones and their derivatives. Instead of applying the classical "de novo" synthetic approaches these benzo[g]isoquinoline-5,10-dione analogs will be prepared by a new "diversity-oriented synthesis" approach in order to optimize their biological activity against chloroquine resistant P. falciparum and M. tuberculosis. The direct introduction of functional groups on the benzo[g]isoquinoline-5,10-dione template molecule, by means of catalytic and/or electrochemical methods holds a central place in the proposed methodology.

Keywords:ORGANIC SYNTHESIS

Disciplines:Organic chemistry