Researchers have developed a breakthrough autofluorescent compound by combining two plant extracts, artemisinin and coumarin. This innovation enables precise imaging in living cells and has been shown to be effective against drug-resistant malaria pathogens, particularly Plasmodium falciparum. The development of these autofluorescent hybrids, which can be observed without changing their effectiveness, represents an important step in the fight against drug-resistant malaria.
Malaria remains one of the world's deadliest infectious diseases. The emergence of drug-resistant malaria parasites requires the continuous development of new drugs.
A research team at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) led by Professor Svetlana B. Tsogoeva has now combined the anti-malarial drug artemisinin with coumarin (which, like artemisinin, is also found in plants) and developed an autofluorescent compound from these two bioactive substances.
This autofluorescence is particularly advantageous because it can be used for live-cell imaging and can show in precise temporal order how a drug works. The team also found that the autofluorescent artemisinin-coumarin mixture was able to destroy a drug-resistant malaria pathogen called Plasmodium palmifolia. They published their findings in the journal Chemical Science.
Artemisinin is a highly effective and commonly used malaria drug ingredient extracted from a plant called Artemisia annua L. Coumarin is a secondary plant compound found in a variety of plants.
In the development of antimalarial drugs, active substances are labeled with fluorescent labels so that imaging techniques can be used to determine in precise chronological order how they act against the malaria pathogen. This fluorescent label has been used for artemisinin.
However, a major drawback of using fluorescent labels is that it changes the way the drug works. This means, for example, that in some cases malaria-infected cells take up drugs such as artemisinin differently after being fluorescently labeled.
The solubility of the drug may also change. This problem has been circumvented by the development of autofluorescent mixtures, which consist of two or more basic compounds that are inherently fluorescent and whose mode of action can be precisely observed using imaging techniques.
The team led by Professor Tsogoeva, Chair of Organic Chemistry, decided to combine artemisinin with bioactive coumarin because coumarin derivatives also have anti-malarial properties. Coumarin derivatives can also be easily chemically altered, making them extremely fluorescent.
The researchers found that not only the mode of action of this first-of-its-kind autofluorescent artemisinin-coumarin mixture could be observed in living red blood cells infected with P. falciparum, but also the biological activity of the artemisinin-coumarin mixture.
Professor Barbara Kappes (Department of Chemical and Bioengineering, Federal University, Brazil) and Dr. Diogo R.M. Moreira (Instituto Gonçalo Moniz, Fiocruz, Bahia, Brazil) jointly discovered that this active preparation is very effective in vitro (in vitro) against Plasmodium falciparum strains that are resistant to chloroquine and other malaria drugs. Most importantly, the new compound was also highly effective against the malaria pathogen in mouse models.
With the arrival of the first autofluorescent artemisinin-coumarin mixture, researchers at FAU hope they have laid the foundation for the development of more autofluorescent drugs to treat malaria and made significant progress in overcoming multidrug resistance to treating malaria.