Dipeptidyl nitrile derivatives have cytostatic effects against Leishmania spp. promastigotes
Copyright © 2019. Published by Elsevier Inc..
Cysteine proteases are involved in critical cell processes to the protozoa from Leishmania genus, and their inhibition is a therapeutic alternative to treat the disease. In this work, derivatives of dipeptidyl nitriles acting as reversible covalent inhibitors of cysteine proteases were studied as cytostatic agents. The proteolytic activity inside the living and lysed parasite cells was quantified using a selective substrate for cysteine proteases (Z-FR-MCA) from Leishmania amazonensis and L. infantum. The overall proteolytic activity of intact cells and even cell extracts was only marginally affected at high concentrations, with the observation of cytostatic activity and cell cycle arrest of promastigotes. However, the cytotoxic effects were only observed for infected J774 macrophages, which impaired further analysis of the amastigote infection. Therefore, the proteolytic inhibition in intact L. amazonensis and L. infantum promastigotes had no relationship to the cytostatic activity, which emphasizes that these dipeptidyl nitriles act through another mechanism of action.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:200 |
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| Enthalten in: |
Experimental parasitology - 200(2019) vom: 20. Mai, Seite 84-91 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Quilles, José C [VerfasserIn] |
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| Links: |
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| Themen: |
Antiprotozoal Agents |
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| Anmerkungen: |
Date Completed 14.05.2019 Date Revised 14.05.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.exppara.2019.04.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM295760125 |
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| 245 | 1 | 0 | |a Dipeptidyl nitrile derivatives have cytostatic effects against Leishmania spp. promastigotes |
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| 500 | |a Date Revised 14.05.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019. Published by Elsevier Inc. | ||
| 520 | |a Cysteine proteases are involved in critical cell processes to the protozoa from Leishmania genus, and their inhibition is a therapeutic alternative to treat the disease. In this work, derivatives of dipeptidyl nitriles acting as reversible covalent inhibitors of cysteine proteases were studied as cytostatic agents. The proteolytic activity inside the living and lysed parasite cells was quantified using a selective substrate for cysteine proteases (Z-FR-MCA) from Leishmania amazonensis and L. infantum. The overall proteolytic activity of intact cells and even cell extracts was only marginally affected at high concentrations, with the observation of cytostatic activity and cell cycle arrest of promastigotes. However, the cytotoxic effects were only observed for infected J774 macrophages, which impaired further analysis of the amastigote infection. Therefore, the proteolytic inhibition in intact L. amazonensis and L. infantum promastigotes had no relationship to the cytostatic activity, which emphasizes that these dipeptidyl nitriles act through another mechanism of action | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell-based assays | |
| 650 | 4 | |a Cytostatic activity | |
| 650 | 4 | |a Dipeptidyl nitriles | |
| 650 | 4 | |a Leishmaniasis | |
| 650 | 7 | |a Antiprotozoal Agents |2 NLM | |
| 650 | 7 | |a Cysteine Proteinase Inhibitors |2 NLM | |
| 650 | 7 | |a Cytostatic Agents |2 NLM | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 700 | 1 | |a Tezuka, Daiane Y |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes, Carla D |e verfasserin |4 aut | |
| 700 | 1 | |a Ribeiro, Fernanda L |e verfasserin |4 aut | |
| 700 | 1 | |a Laughton, Charles A |e verfasserin |4 aut | |
| 700 | 1 | |a de Albuquerque, Sérgio |e verfasserin |4 aut | |
| 700 | 1 | |a Montanari, Carlos A |e verfasserin |4 aut | |
| 700 | 1 | |a Leitão, Andrei |e verfasserin |4 aut | |
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