Identification of COMT and ErmC inhibitors by using a microplate assay in combination with library focusing by virtual screening

K Kreander; M Kurkela; A Siiskonen; P Vuorela; P Tammela

Identification of COMT and ErmC inhibitors by using a microplate assay in combination with library focusing by virtual screening

Pharmazie. 2006 Mar;61(3):247-8.

Authors

K Kreander¹, M Kurkela, A Siiskonen, P Vuorela, P Tammela

Affiliation

¹ Drug Discovery and Development Technology Center (DDTC), Faculty of Pharmacy, University of Helsinki, Finland.

PMID: 16599271

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catechol O-Methyltransferase Inhibitors*
Catechols / antagonists & inhibitors*
Computer Simulation
Dimethyl Sulfoxide / pharmacology
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors / pharmacology*
Models, Molecular
Structure-Activity Relationship

Substances

Catechol O-Methyltransferase Inhibitors
Catechols
Enzyme Inhibitors
Dimethyl Sulfoxide