Project Lead(s): Dylan Pillai
Close to 600,000 people die from malaria infection annually, with Sub-Saharan Africa suffering the brunt of the mortality.
A contributing factor is the emergence of antimalarial resistance to the best drugs available, including artemisinin and its partner drugs, such as piperaquine.
A bold approach has been proposed to identify novel agents that reverse resistance to mainstay antimalarial drugs, such as artemisinin.
These new reversal agents will target heat shock protein 90 that can restore antimalarial activity.
The team sought to identify an antimalarial compound derived from a West African traditional medicine demonstrated in pre-clinical trials to have potent activity.
It is hoped this compound (harmine derivative 21A), which targets heat shock protein 90 (Hsp90), can forestall the rising tide of artemisinin resistance.
This modification of harmine (21A) showed the capacity to inhibit Hsp90, kill malaria parasites in the test tube, and prolong survival of mice when used in combination with artemisinin, without exhibiting untoward toxicity.
The plan is to conduct further trials with 21A-like derivatives after patent protection is achieved.
Results of this work were discussed in conference presentations and were being prepared for publication.