4-Aminoquinoline Hybridization Concept as Alternative Antiplasmodial Agent

The emergence of parasitic strains' resistant to almost all antimalarial drugs has prompted scientists to study more effective alternative mechanisms of action. Current antimalarial treatment is limited due to poor drug bioavailability, high drug toxicity, and low aqueous solubility. Hybridization is an exciting strategy in antimalarial drug discovery. The 4-aminoquinoline framework has been targeted in the design of various antiplasmodial agents because its synthesis is low cost, safe and has been used over the past 20 years. The discovery of antiplasmodial hybrids using the 4-aminoquinoline framework and various moieties such as artemisinin, piperidine, indoline, and pyrimidine have shown good antiplasmodial activity. However, these hybrids are still not fully developed for clinical trials. This literature review summarises the findings of antiplasmodial hybrids published over the past eleven years (2011-2021). The advantages and disadvantages of hybridization as a substitute for existing antiplasmodial agents are discussed. This review reports that 4-aminoquinoline hybrids had comparable or better in vitro antiplasmodial activity than the chloroquine prophylaxis treatment. Class IV quinoline hybrids were the most frequently studied and obtained in this study over the past eleven years. The lack of detailed preclinical data on the synthesised hybrids has hampered further studies in clinical trials.

Automated summary

The emergence of parasitic strains resistant to most antimalarial drugs has led to the exploration of more effective alternative mechanisms. Hybridization, particularly using the 4-aminoquinoline framework, has shown promise in the development of new antimalarial agents. However, further development and clinical trials are needed for these hybrids, and the lack of detailed preclinical data has hindered progress.