AsianScientist (Dec. 31, 2018) – A team of researchers from the Singapore University of Technology and Design (SUTD) and Nanyang Technological University (NTU), Singapore, has developed a class of gold-containing molecules that impair the malaria parasite’s metabolic function, leading to parasite death. Their findings are published in the journal Dalton Transactions.
Despite concerted efforts to eliminate malaria, the deadly disease remains a major health threat to the developing world. The causative agent, a parasite known as Plasmodium, is able to establish and sustain infections in humans, leading to complex clinical manifestations.
Making matters worse, the parasite is gaining resistance to a wide range of clinical antimalarial drugs available in the market. There is thus an urgent need to develop new and better antimalarials.
In this study, researchers in Singapore developed a panel of chemical compounds categorized as ferrocenyl phosphines that target Plasmodium. The NTU team, led by Dr. Sumod A. Pullarkat, synthesized the small molecule inhibitors, which were subsequently tested for antimalarial effects by Assistant Professor Rajesh Chandramohanadas’ team at SUTD.
Among the various compounds synthesized, the scientists identified G3—a gold-complexed ferrocinyl phosphine derivative—as being the most potent against metabolically active parasites. G3 compromised the formation of digestive vacuoles in Plasmodium, which prevented the parasite from degrading human hemoglobin, which it needs for growth and proliferation.
“From a chemist’s point of view, the step-by-step introduction of pharmacophores in a novel chemical framework permitted us the opportunity to systematically evaluate the function of each incorporated component in rendering antimalarial activity, across various stages of parasite development,” said Pullarkat.
Chandramohanadas added that obtaining chemically-diverse small molecules that interfere with hemoglobin metabolism—a hallmark of malaria infection—could result in novel antimalarials that target drug-resistant forms of Plasmodium.
The article can be found at: Subramanian et al. (2018) Evaluation of Ferrocenyl Phosphines as Potent Antimalarials Targeting the Digestive Vacuole Function of Plasmodium falciparum.
Source: Singapore University of Technology and Design.
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