An Overview of Available Antimalarials: Discovery, Mode of Action and Drug Resistance

Abstract

: Malaria is one of the three most deadly infectious diseases in the world and seriously endangers human health and life. To reduce the public health burden of this disease, scientists have focused on the discovery and development of effective antimalarial drugs, from quinine and chloroquine to antifolates and artemisinin and its derivatives, which all play a profound role in the treatment of malaria. However, drug-resistant strains of Plasmodium falciparum have emerged due to frequent use of antimalarials and have become increasingly resistant to existing antimalarial drugs , which had caused disastrous consequences in the world. In particular, artemisinin resistance is of greatest concern which was reported in 2008. Resistance to artenisinins has been a major obstacles for malaria control and current efforts to curb artemisinin resistance have not been successful. Based on current suitation it is urgent to develop more effective new antimalarials with distinct targets from conventional antimalarials in the world which could facilitate to minimize the phenomenon of drug resistance. This review aims to summarize different kinds of antimalarial therapeutic efficacy, mechanisms of action and resistance and proposes new solutions aiming towards further improvement of malaria elimination.

Beyond Anti-viral Effects of Chloroquine/Hydroxychloroquine

“…Chloroquine (CQ) and hydroxychloroquine (HCQ) are “old” drugs but are still widely used in very diverse situations, including infectious diseases ( 1 – 3 ), rheumatic/inflammatory diseases ( 4 ), or in clinical research protocols as add-on cancer therapy ( 5 ). Indeed, they are cheap and safe considering rare effective ocular toxicity (<2%) and acute cardiac toxicity.…”

Evaluation of Antimalarial Potential of Aqueous Crude Gymnema Inodorum Leaf Extract against Plasmodium berghei Infection in Mice

“…The strategy for malaria and case management have largely relied and mainly focus on antimalarial drugs [ 3 ]. However, the emergence of Plasmodium parasite resistance to currently available antimalarial drugs such as amodiaquine, mefloquine, quinine, chloroquine, sulfadoxine-pyrimethamine, and artemisinin derivatives has been reported [ 4 ]. Therefore, searching for new and novel antimalarial compounds that are safe, effective, and affordable are urgently needed.…”

Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19

“…One is the transporter protein P-glycoprotein (P-gp/ABCB1) homolog 1 (Pgh1) on the membrane of vacuoles of the parasite, which is encoded by a multidrug resistance (MDR) gene, the Plasmodium falciparum multidrug resistance-1 ( pfmdr1 ) gene on chromosome 5 ( Skrzypek & Callaghan, 2017 ). As Pgh1 is a homolog of the ATP- binding cassette (ABC) transporter P-gp, which contributes to the cross-cytomembrane transport of substrates out of cells ( Kathawala, Gupta, Ashby Jr., & Chen, 2015 ), Pgh1 may have a similar function pumping CQ and CQ analogs from the cytoplasm to the vacuoles ( Anderson et al, 2005 ; Jovel, Björkman, Roper, Mårtensson, & Ursing, 2017 ; Tang, Ye, Huang, & Zheng, 2020 ). Under the pressure of CQ/HCQ, the pfmdr1 gene has many geographical mutations to gain resistance ( Skrzypek & Callaghan, 2017 ).…”