Anti-infectives: can cellular screening deliver?

Area of Science:

• Drug discovery and development
• Infectious diseases
• Medicinal chemistry

Background:

• Emerging infectious diseases and multidrug resistance necessitate novel therapeutic strategies.
• The shift towards target-based drug discovery has yielded limited success.
• Phenotypic, cell-based screening is experiencing a resurgence, leading to clinical candidates.

Purpose of the Study:

• To review the success of the cell-based approach in anti-infective drug discovery.
• To highlight specific examples of drugs identified through cell-based screening.
• To discuss challenges and propose improvements for the cell-based approach.

Main Methods:

• Review of literature on cell-based screening for anti-infectives.
• Detailed analysis of three successful drug classes: spiroindolone, thiazolidinone, and diarylquinoline.
• Examination of their identification, mechanism of action, and chemical structures.

Main Results:

• Spiroindolone, thiazolidinone, and diarylquinoline are effective against malaria, hepatitis C virus, and tuberculosis, respectively.
• These examples demonstrate the viability of the cell-based approach.
• Common structural features contributing to efficacy were identified.

Conclusions:

• The cell-based approach is a valuable strategy for identifying novel anti-infective agents.
• Challenges in phenotypic lead finding can be addressed by using synthetic natural-product-like compound collections.
• This approach can improve hit validation and accelerate the development of new therapies.