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ID: ALA4219198
Journal: Bioorg Med Chem Lett
Title: Peptidomimetic nitrile inhibitors of malarial protease falcipain-2 with high selectivity against human cathepsins.
Authors: Nizi E, Sferrazza A, Fabbrini D, Nardi V, Andreini M, Graziani R, Gennari N, Bresciani A, Paonessa G, Harper S.
Abstract: Falcipain-2 (FP2) is an essential enzyme in the lifecycle of malaria parasites such as Plasmodium falciparum, and its inhibition is viewed as an attractive mechanism of action for new anti-malarial agents. Selective inhibition of FP2 with respect to a family of human cysteine proteases (that include cathepsins B, K, L and S) is likely to be required for the development of agents targeting FP2. Here we describe a series of P2-modified aminonitrile based inhibitors of FP2 that provide a clear strategy toward addressing selectivity for the P. falciparum and show that it can provide potent FP2 inhibitors with strong selectivity against all four of these human cathepsin isoforms.
CiteXplore: 29615344