Quinolines and structurally related heterocycles as antimalarials

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Parasitology

Background:

• The quinoline scaffold is a core structure in numerous synthetic and natural pharmacologically active compounds.
• Chloroquine, a prominent quinoline-based drug, was instrumental in malaria control for decades.
• Other notable quinoline antimalarials include quinine, amodiaquine, piperaquine, primaquine, and mefloquine, targeting various parasite life stages.

Purpose of the Study:

• To provide a comprehensive literature review on quinolines and similar heterocycles in malaria treatment.
• To consolidate advances in the field over the last ten years.
• To discuss biological activities, structure-activity relationships, and biochemical pathways of diverse quinoline derivatives.

Main Methods:

• Literature compilation and review of scientific publications.
• Subdivision of the review into eight thematic sub-headings.
• Discussion of specific quinoline classes: 4-aminoquinolines, 4-anilinoquinolines, 8-aminoquinolines, natural quinolines, quinolones, isoquinolines, tetrahydroquinolines, ring-modified quinolines, and miscellaneous quinolines.

Main Results:

• Identification of diverse quinoline derivatives with antimalarial potential.
• Elucidation of structure-activity relationships for various quinoline subclasses.
• Exploration of potential biochemical mechanisms of action against the malaria parasite.

Conclusions:

• Quinolines and related heterocycles remain a vital area of research for novel antimalarial drug discovery.
• Recent advances highlight the continued importance of exploring these scaffolds for new therapeutic strategies.
• Understanding SAR and biochemical pathways is crucial for developing next-generation antimalarials.