title: Anti-infectives: can cellular screening deliver?
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.
authors: Experimental Therapeutics Center, Singapore.
authors: Thomas H
authors: TH
authors: Keller
authors: Pei-Yong
authors: PY
authors: Shi
authors: Qing-Yin
authors: QY
authors: Wang
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D016174:Hepacivirus / Q000187:drug effects; D057166:High-Throughput Screening Assays; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D000995:Antitubercular Agents