Affiliation:
1. Laboratory of Medicinal Chemistry, CIRM, University of Liège, Liège, Belgium
2. Laboratory of Pharmacognosy, CIRM, University of Liège, Liège, Belgium
Abstract
Background:
Malaria was one of the deadliest infectious diseases in 2021. Indeed, this infection,
mostly caused by a protozoan called Plasmodium falciparum, is responsible for more than 200 million
cases and around 400 000 related deaths annually, mainly in Africa. Despite the availability of effective
drugs, the number of patients has increased since 2015, which could be due to parasite resistance as
well as resistance in the pathogen's vectors, Anopheles mosquitoes. Consequently, it is necessary to search
for new alternative treatments.
Methods:
Polyphenols, more precisely small phenolic acids, could represent a good starting point for new
antimalarials. Indeed, these molecules, including caffeic acid (1), possess several pharmacological activities
and an interesting pharmacokinetic profile. Therefore, we have developed several small derivatives of
this scaffold to define the potential pharmacophore responsible for the antiplasmodial properties.
Results:
A good to low activity on Plasmodium falciparum (IC50 = 16-241 μM) was observed, especially
for the small ester derivatives (2-6). These molecules were good antiplasmodials compared to their mother
compound (IC50 = 80 μM) and showed selectivity against human cells. These structures have also highlighted
the need for catechol and carboxyl moieties in the anti-Plasmodium effect.
Conclusion:
None of the synthetic caffeate derivatives reported here seemed sufficiently effective to become
a potential antimalarial (IC50 < 1 μM). However, the significant increase of their efficacy on the
malarial agent and the selectivity to human cells highlighted their potential as new leads for future developments.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
Reference83 articles.
1. Center for Disease Control. Available from: (Accessed on: Jan 27, 2021).
2. World Health Organization. World Malaria Report 2020, 2020
3. World Health Organisation. Malaria, Available from: (Accessed on: Nov 10, 2020).2022
4. Center for disease control. Malaria’s impact worldwide. Available from: (Accessed on: Jan 27, 2021).
5. Center for disease control. Drug resistance in the malaria-endemic
world. Available from: (Accessed on: Jan 27,
2021).
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