Anti-infectives: Can cellular screening deliver?

Thomas H. Keller, Pei Yong Shi, Qing Yin Wang

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

In an era of emerging and reemerging infectious diseases, and increasing multidrug resistance, the need to identify novel therapy is imperative. Unfortunately, the recent shift of the drug discovery paradigm from cellular screening to target-based approaches has not delivered the anticipated benefits. A recent renaissance of the traditional cell-based approach, on the other hand, has yielded several clinical candidates. Three successful examples are illustrated in this review, namely spiroindolone, thiazolidinone, and diarylquinoline for the treatment of malaria, hepatitis C virus, and tuberculosis, respectively. We describe in detail their identification, mechanism of action (MoA), and common features in the chemical structures. The challenges of the cell-based approach for anti-infective drug discovery are also discussed. We propose a shift from standard libraries to synthetic natural-product-like compound collections to improve the success of phenotypic lead finding and to facilitate the validation of hits.

Original languageEnglish (US)
Pages (from-to)529-533
Number of pages5
JournalCurrent Opinion in Chemical Biology
Volume15
Issue number4
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

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