title: Rhodanine as a scaffold in drug discovery: a critical review of its biological activities and mechanisms of target modulation.
abstract: BACKGROUND
  Rhodanine-based compounds have been associated with numerous biological activities. After many years of research in drug discovery, they have gained a reputation as being pan assay interference compounds (PAINS) and frequent hitters in screening campaigns. Rhodanine-based compounds are also aggregators that can non-specifically interact with target proteins as well as Michael acceptors and interfere photometrically in biological assays due to their color.
  
  
  METHODS
  The authors review the recently reported biological activities of rhodanine-based compounds. Furthermore, the article provides details of their synthesis and occurrence in compound libraries through high-throughput screening (HTS) and virtual high-throughput screening (VHTS). Additionally, the authors provide the reader with possible mechanisms of non-specific target modulation, analysis of the crystal structures of enzyme-rhodanine complexes and a comparison of rhodanine and thiazolidine-2,4-dione moieties.
  
  
  CONCLUSIONS
  The biological activity of compounds possessing a rhodanine moiety should be considered very critically despite the convincing data obtained in biological assays. In addition to the lack of selectivity, unusual structure-activity relationship profiles and safety and specificity problems mean that rhodanines are generally not optimizable.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomašić
authors.forename: Lucija
authors.initials: L
authors.lastname: Peterlin Mašič
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012236:Rhodanine / Q000737:chemistry* / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000032:analysis; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D012236:Rhodanine