Novel inhibitors of mycobacterium tuberculosis complex cytochrome P450 CYP121

摘要

The present invention relates to the identification of the cyclodipeptide cyclo(L-Tyr-L-Tyr) as substrate of CYP121 from Mycobacterium tuberculosis, to the crystal structures of CYP121 complexed either with cyclo(L-Tyr-L-Tyr) or with other cyclodipeptides, to the use of these structures in rational drug design methods to generate cyclodipeptide-based molecules that could inhibit CYP121 activity, and to the design of new anti-Mycobacterium tuberculosis agents based on the DKP scaffold.