Discovery and Development of Antimalarial Drug Resistance Reversal Agents
- Authors: Phanankosi Moyo1, Vinesh Maharaj2, Sephora M. Mutombo3, Warren Andrew Andayi4, Linda Amoah5, Kathithileni M. Kalili6, Kwame Kumi Asare7, Cynthia Amaning Danquah8
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View Affiliations Hide AffiliationsAffiliations: 1 Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0028, South Africa 2 Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0028, South Africa 3 Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0028, South Africa 4 Department of Physical and Biological Sciences, Muranga University of Technology, Muranga, Kenya 5 Immunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana 6 Department of Physics, Chemistry & Material Science, University of Namibia, Private Bag 13301, 340 Mandume Ndemufayo Avenue, Pionierspark, Windhoek, Namibia 7 Department of Biomedical Sciences, School of Allied Health Sciences, College of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana 8 Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Ghana
- Source: Frontiers in Anti-Infective Drug Discovery : Volume 10 , pp 24-73
- Publication Date: June 2024
- Language: English
Discovery and Development of Antimalarial Drug Resistance Reversal Agents, Page 1 of 1
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Despite the meritorious measures taken to curb the malaria scourge in the last two decades, the drug-resistance phenomenon threatens to reverse the gains made. Evidence of partial resistance against the first-line antimalarial drugs, the artemisininbased combination therapies, in Africa, a region that accounts for 95% of global malaria cases, has aroused fears that it could spread fast and significantly jeopardise malaria control and eradication efforts. While the antimalarial drug discovery pipeline has several, encouraging candidates emerging through it, unfortunately, the attrition rate is high, with some candidates failing either in preclinical studies or clinical trials. Moreover, the rate of emergence of drug-resistant Plasmodium parasite strains far exceeds that of the drug discovery and development process. These challenges demand novel strategies to complement the discovery and development of new therapeutics. One such strategy is the reversal of Plasmodium falciparum resistance to old antimalarials by combining these drugs with agents that specifically target drugresistance mechanisms. This strategy has been successfully used in the antibiotics field, with a classical successful example being the amoxicillin and clavulanic acid combination. In this chapter, we present a case for the need to discover and develop antimalarial drug-resistance reversal agents to prolong the efficacy and use of currently available antimalarial quinoline drugs as well as the re-use of old antimalarial quinoline drugs that have been rendered ineffective by drug-resistance. Furthermore, we provide an overview of noteworthy significant innovations that have been made in the field in search for antimalaria drug-resistance reversal agents. We conclude by providing perspectives on how these efforts can be expedited.
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