Virtual screening of antiplasmodial natural products using CADD against pfDHODH

Malaria is a global health concern with the highest morbidities being reported in sub-Saharan Africa. It is a public health concern given the rise of antimalarial drug resistance in the plasmodium parasite whereby P. falciparum which causes the most severe malaria has shown resistance to nearly all antimalarial drugs.

This calls for the development of new antimalarial drugs; however, the traditional random synthesis/isolation and screening method of drug discovery is a slow and expensive process hence the need for design of drugs that have a high probability of success. Computer aided drug design (CADD) employs computing power to express molecular properties thus allowing a sizeable amount of molecules to be virtually screened at a go. In this research project, OpenEye CADD software suite was used in docking and shape matching techniques in order to screen a total of 360 antiplasmodial natural products against Plasmodium falciparum dihydroorotate dehydrogenase (pfDHODH) for the establishment of a potential lead antiplasmodial compound. pfDHODH is an enzyme that plays a key role in the de novo biochemical synthesis of DNA making it an attractive antimalarial drug target.

The results of this study show that 1,6-dihydroxy-7-methyl-3,10-dioxo-anthracen-9-olate (Demethylmacrosporine) an anthraquinone isolated from Rumex obtusifolius  (Polygonaceae) is a potential lead compound for antimalarial drug development targeting pfDHODH . The results also show the most favourable pose that should be assumed by the compound for effective inhibition of the enzyme.

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