title: Identification of COMT and ErmC inhibitors by using a microplate assay in combination with library focusing by virtual screening.
abstract: The paper describes a process of facilitated screening by using a combination of molecular modelling and a 96-well microplate assay for the identification of novel inhibitors of catechol-O-methyltransferase (COMT) and bacteria expressing ErmC. With the help of virtual screening the number of compounds processed in the in vitro screening assay was reduced from over 200,000 to 49. Out of the 49, two structurally very similar compounds were identified as confirmed hits with reasonable activity (IC50 values of 26 and 73 microM) and thus as potential core structures for further drug design and development.
authors.affiliation: Drug Discovery and Development Technology Center (DDTC), Faculty of Pharmacy, University of Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Kreander
authors.forename: M
authors.initials: M
authors.lastname: Kurkela
authors.forename: A
authors.initials: A
authors.lastname: Siiskonen
authors.forename: P
authors.initials: P
authors.lastname: Vuorela
authors.forename: P
authors.initials: P
authors.lastname: Tammela
mesh_terms: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D004121:Dimethyl Sulfoxide