Privileged small molecules against neglected tropical diseases: A perspective from structure activity relationships

Area of Science:

• Medicinal Chemistry
• Parasitology
• Drug Discovery

Background:

• Neglected tropical diseases (NTDs) pose a significant global health burden, affecting over 1.5 billion people.
• Key parasitic NTDs like leishmaniasis, Chagas disease (CD), and human African trypanosomiasis (HAT) cause substantial morbidity and mortality, especially in impoverished regions.
• Existing anti-NTD drugs face challenges including drug resistance, lack of vaccines, limited efficacy, and adverse effects.

Purpose of the Study:

• To review recent advancements in the development of anti-infective small molecules against parasitic NTDs.
• To analyze these agents from a Structure-Activity Relationship (SAR) perspective.
• To explore emerging strategies for expanding the therapeutic scope of anti-NTD agents.

Main Methods:

• Literature review focusing on recent scientific publications and epidemiological reports.
• Analysis of chemical structures of anti-NTD agents, particularly nitrogen, sulfur, and oxygen-based heterocycles.
• Examination of Structure-Activity Relationship (SAR) data for identified compounds.

Main Results:

• Numerous small molecules, often featuring privileged heterocyclic scaffolds, have shown promise against parasitic NTDs.
• SAR studies are crucial for understanding and optimizing the efficacy of these anti-infective agents.
• Emerging strategies aim to overcome limitations of current therapies and broaden treatment options.

Conclusions:

• The development of novel small molecules with optimized SAR is critical for addressing the NTD crisis.
• Continued research into heterocyclic chemistry and innovative therapeutic strategies is essential for effective NTD control.
• Addressing drug resistance and improving drug profiles are key priorities for future anti-NTD drug discovery.