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International Journal of Drug Development and Research

  • ISSN: 0975-9344
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Design, synthesis and evaluation of novel leads for drug-resistant malaria

17th Edition of International Conference and Exhibition on Pharmaceutics and Novel Drug Delivery Systems
October 04-06, 2018 Moscow, Russia

Rachael Magwaza

The University of Manchester, UK

Posters & Accepted Abstracts: Int J Drug Dev & Res

Abstract:

Malaria is caused by parasite infection of the genus Plasmodium. Human infection is caused by one of five Plasmodium species including falciparum, malariae, knowlesi, vivax and ovale. P. falciparum is associated with the most severe form of malaria and responsible for approximately 400,000 deaths per year. A number of antimalarial drugs are currently used to treat malaria. However, P. falciparum, which is responsible for mortality especially in Eastern and Southern Africa, has developed resistance to all currently used drugs. Hence, there is a great need for the development of new drugs for malaria. Here, we report non-symmetrical furan-amidines as novel antimalarial leads. The non-symmetrical furan-amidines were originally designed and shown to be inhibitors of NRH:quinone oxidoreductase 2 (NQO2), a potential therapeutic target in cancer chemotherapy. The malaria parasite P. falciparum contains an enzyme that has similar activity to NQO2 called PfNDH2, therefore the non-symmetrical furan-amidines were tested against Plasmodium. The most active furan-amidines showed IC50 values in the nanomolar range for the inhibition of P. falciparum erythrocyte development. Interestingly, upon screening, the most active non-symmetrical furan-amidines showed poor inhibition of PfNDH2. In addition, the non-symmetrical furan-amidines showed very low binding affinities towards DNA in comparison to the known symmetrical furan-amidine (DB75), which is a known DNA intercalator. This confirmed that the non-symmetrical furan-amidines are not DNA intercalators and do not target the PfNDH2 enzyme. Synthesis of further novel non-symmetrical furan-amidines and their target identification is ongoing.

Biography :

E-mail:

rachael.magwaza@manchester.ac.uk

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