Peptidomimetic nitrile inhibitors of malarial protease falcipain-2 with high selectivity against human cathepsins |
| |
Authors: | Emanuela Nizi Alessio Sferrazza Danilo Fabbrini Valentina Nardi Matteo Andreini Rita Graziani Nadia Gennari Alberto Bresciani Giacomo Paonessa Steven Harper |
| |
Affiliation: | 1. Department of Chemistry, IRBM Science Park, Via Pontina km 30, 600, Pomezia 00071, Rome, Italy;2. Department of Biology, IRBM Science Park, Via Pontina km 30, 600, Pomezia 00071, Rome, Italy |
| |
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. |
| |
Keywords: | Malaria Falcipain-2 Peptidomimetic-nitrile 3-Pyridine Selective |
本文献已被 ScienceDirect 等数据库收录! |
|