Abstract
Malaria is among the deadliest infectious diseases in the world caused by Plasmodium parasites. Due to the high complexity of the parasite’s life cycle, we partly depend on antimalarial drugs to fight this disease. However, the emergence of resistance, mainly by Plasmodium falciparum, has dethroned most of the antimalarials developed to date. Given recent reports of resistance to artemisinin combination therapies, first-line treatment currently recommended by the World Health Organization, in Western Cambodia and across the Greater Mekong sub-region, it seems very likely that artemisinin and its derivatives will follow the same path of other antimalarial drugs. Consequently, novel, safe and efficient antimalarial drugs are urgently needed. One fast and low-cost strategy to accelerate antimalarial development is by recycling classical pharmacophores. Quinacrine, an acridine-based compound and the first clinically tested synthetic antimalarial drug with potent blood schizonticide but serious side effects, has attracted attention due to its broad spectrum of biological activity. In this sense, the present review will focus on efforts made in the last 20 years for the development of more efficient, safer and affordable antimalarial compounds, through recycling the classical quinacrine drug.
Highlights
A century has elapsed since Laveran described Plasmodium parasites and Ross confirmed that they were transmitted by mosquitoes [1]
We have been witnessing the decrease in malaria burden over the last decade, prospects for malaria eradication are threatened by resistance to artemisinin-based combination therapies, the current first-line antimalarial treatment [3], urging the development of new classes of antimalarials
Elimination efforts require identification of new drug classes acting at multiple stages of the parasite life cycle
Summary
A century has elapsed since Laveran described Plasmodium parasites and Ross confirmed that they were transmitted by mosquitoes [1]. While a vaccine remains elusive, we depend on chemotherapeutic agents to both treat infections and prevent disease. To eradicate malaria, it is mandatory to develop compounds that block parasite transmission, cure the asymptomatic hepatic infection and clear the latent forms in the liver [5]. Elimination efforts require identification of new drug classes acting at multiple stages of the parasite life cycle. One strategy to accelerate development of antimalarials is to recycle known drug scaffolds [4]. Different modes of action seem to be exerted by AC derivatives depending on their therapeutic targets, the most consensual mechanism of action (MOA) of AC analogues against different diseases is interaction with DNA [8]. Other MOAs have been suggested to elucidate. Other MOAs have been suggested to elucidate the tahnetiamnatliamriaallaaricatilvaictytivofitAy CofdAerCivdateirvievsa,tsiuvcehs,assuicnhhiabsitinohniobfittihoenpoafrathsietep’sar(ia)stiytep’es I(Ii)totyppoie-.
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