کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1936682 | 1050699 | 2007 | 7 صفحه PDF | دانلود رایگان |

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 Kd of 11.2 ± 9.2 μM and an IC50 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.
Journal: Biochemical and Biophysical Research Communications - Volume 363, Issue 4, 30 November 2007, Pages 1013–1019