Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors |
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| Authors: | Roberta Ettari Santo Previti Sandro Cosconati Jochen Kesselring Tanja Schirmeister Silvana Grasso |
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| Affiliation: | 1. Dipartimento Di Scienze Del Farmaco E Dei Prodotti per La Salute, University of Messina, Messina, Italy, rettari@unime.it;3. Dipartimento Di Scienze Del Farmaco E Dei Prodotti per La Salute, University of Messina, Messina, Italy,;4. DiSTABiF, Second University of Naples, Naples, Italy,;5. Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany, and;6. Dipartimento Di Scienze Chimiche, University of Messina, Messina, Italy |
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| Abstract: | Novel rhodesain inhibitors were developed by combining an enantiomerically pure 3-bromoisoxazoline warhead with a 1,4-benzodiazepine scaffold as specific recognition moiety. All compounds were proven to inhibit rhodesain with Ki values in the low-micromolar range. Their activity towards rhodesain was found to be coupled to an in vitro antitrypanosomal activity, with IC50 values ranging from the mid-micromolar to a low-micromolar value for the most active rhodesain inhibitor (R,S,S)-3. All compounds showed a good selectivity against the target enzyme since all of them were proven to be poor inhibitors of human cathepsin L. |
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| Keywords: | Peptidomimetics rhodesain trypanosoma |
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