Abstract
Cyclophilins, which are found in all cellular compartments and with diverse biological roles, are now drug targets for a number of diseases including HIV infection, malaria and ischaemia. We used the database-mining program LIDAEUS and in silico screening to discover the dimedone family of inhibitors which show a conserved ‘ball and socket’ binding mode with a dimethyl group in the hydrophobic binding pocket of human cyclophilin A (CypA) mimicking a key interaction of the natural inhibitor cyclosporin A (CsA). The most potent derivative binds CypA with a K d of 11.2 ± 9.2 μM and an IC 50 for activity against Caenorhabditis elegans (C. elegans) of 190 μM compared to 28 μM for CsA. These dimedone analogues provide a new scaffold for the synthesis of families of peptidomimetic molecules with potential activity against HIV, malaria, and helminth parasite infections.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochemical and Biophysical Research Communications
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
