Malaria: The World’s Biggest Killer
Manuel Ruiz and his team have been working on new treatments for Malaria, at Merck. I created this cover in support of his Merck research on the malaria drug code-named WM382. WM382 targets multiple stages of the malaria parasite life cycle, inhibiting essential enzymes, as a dual inhibitor of plasmepsin IX and plasmepsin X.
Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected mosquitoes. The disease is widespread in tropical and subtropical regions, particularly in Africa, Asia, and Latin America. According to the World Health Organization, malaria is one of the top five causes of death in children under five years old. In 2021, there were an estimated 247 million cases of malaria worldwide, and 619,000 deaths. About 95% of malaria cases and deaths occur in Africa. Children under the age of 5 are particularly vulnerable. In 2021, they accounted for about 80% of all malaria deaths in Africa.
The Search for New Antimalarial Drugs
The control of malaria relies on a combination of vector control (such as insecticide-treated bed nets) and treatment of infected individuals with antimalarial drugs. However, the emergence and spread of resistance to both insecticides and antimalarial drugs is a major challenge. New antimalarial drugs with novel mechanisms of action are urgently needed to combat drug resistance and to achieve the goal of malaria eradication.
A New Hope for Malaria Treatment
In this context, the discovery of a new class of antimalarial compounds, the pyrimidine derivatives, is a major breakthrough. These compounds have shown to fight well against Plasmodium falciparum, one of the parasites that cause malaria in humans. In particular, the compound “WM382” has demonstrated exceptional efficacy in preclinical studies.
The Challenge of Synthesizing WM382
However, the conventional synthesis of WM382 is inefficient and involves many steps. To address this problem, the authors of this paper explored a new approach to synthesize WM382, which involves a series of reactions that gradually add chemical groups and modify the structure of the molecule, eventually leading to the formation of the desired WM382 compound.
A More Efficient and Practical Synthesis of WM382
The authors were able to synthesize WM382 in 11 steps with an overall yield of 7%. This is a significant improvement over the conventional synthesis, which requires 17 steps and has an overall yield of only 1%. The new synthesis is also more convergent, meaning that it involves fewer steps in the longest linear sequence, making it better for large-scale production.
The Promise of WM382
The new synthesis of WM382 is a major step forward in the fight against malaria. This compound has the potential to be a safe, effective, and affordable treatment for malaria. With further development, WM382 could help to save millions of lives.
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