Drug Combination Studies of the Dipeptide Nitrile CD24 with Curcumin: A New Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense

Publication type:
Journal article
Metadata:
Autoren
  • Carla Di Chio
  • Santo Previti
  • Fabiola De Luca
  • Marta Bogacz
  • Collin Zimmer
  • Annika Wagner
  • Tanja Schirmeister
  • Maria Zappala
  • Roberta Ettari
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000887415700001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3390/ijms232214470
eISSN
1422-0067
Externe Identifier
  • Clarivate Analytics Document Solution ID: 6K3OJ
  • PubMed Identifier: 36430948
Ausgabe der Veröffentlichung
22
Zeitschrift
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Schlüsselwörter
  • cysteine protease
  • rhodesain inhibitors
  • dipeptide nitrile
  • curcumin
  • combination studies
Artikelnummer
ARTN 14470
Datum der Veröffentlichung
2022
Status
Published
Titel
Drug Combination Studies of the Dipeptide Nitrile CD24 with Curcumin: A New Strategy to Synergistically Inhibit Rhodesain of <i>Trypanosoma brucei rhodesiense</i>
Sub types
  • Article
Ausgabe der Zeitschrift
23

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>Rhodesain is a cysteine protease that is crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite causing the lethal form of Human African Trypanosomiasis. CD24 is a recently developed synthetic inhibitor of rhodesain, characterized by a nanomolar affinity towards the trypanosomal protease (Ki = 16 nM), and acting as a competitive inhibitor. In the present work, we carried out a combination study of CD24 with curcumin, the multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. By applying the Chou and Talalay method, we obtained an initial additive effect at IC50 (fa = 0.5, Combination Index = 1), while for the most relevant fa values, ranging from 0.6 to 1, i.e., from 60% to 100% of rhodesain inhibition, we obtained a combination index &lt; 1, thus suggesting that an increasingly synergistic action occurred for the combination of the synthetic inhibitor CD24 and curcumin. Furthermore, the combination of the two inhibitors showed an antitrypanosomal activity better than that of CD24 alone (EC50 = 4.85 µM and 10.1 µM for the combination and CD24, respectively), thus suggesting the use of the two inhibitors in combination is desirable.</jats:p>
Autoren
  • Carla Di Chio
  • Santo Previti
  • Fabiola De Luca
  • Marta Bogacz
  • Collin Zimmer
  • Annika Wagner
  • Tanja Schirmeister
  • Maria Zappalà
  • Roberta Ettari
DOI
10.3390/ijms232214470
eISSN
1422-0067
Ausgabe der Veröffentlichung
22
Zeitschrift
International Journal of Molecular Sciences
Sprache
en
Online publication date
2022
Paginierung
14470 - 14470
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/ijms232214470
Datum der Datenerfassung
2023
Titel
Drug Combination Studies of the Dipeptide Nitrile CD24 with Curcumin: A New Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense
Ausgabe der Zeitschrift
23

Data source: Crossref

Abstract
Rhodesain is a cysteine protease that is crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite causing the lethal form of Human African Trypanosomiasis. CD24 is a recently developed synthetic inhibitor of rhodesain, characterized by a nanomolar affinity towards the trypanosomal protease (Ki = 16 nM), and acting as a competitive inhibitor. In the present work, we carried out a combination study of CD24 with curcumin, the multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. By applying the Chou and Talalay method, we obtained an initial additive effect at IC50 (fa = 0.5, Combination Index = 1), while for the most relevant fa values, ranging from 0.6 to 1, i.e., from 60% to 100% of rhodesain inhibition, we obtained a combination index < 1, thus suggesting that an increasingly synergistic action occurred for the combination of the synthetic inhibitor CD24 and curcumin. Furthermore, the combination of the two inhibitors showed an antitrypanosomal activity better than that of CD24 alone (EC50 = 4.85 µM and 10.1 µM for the combination and CD24, respectively), thus suggesting the use of the two inhibitors in combination is desirable.
Addresses
  • Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d'Alcontres 31, 98166 Messina, Italy.
Autoren
  • Carla Di Chio
  • Santo Previti
  • Fabiola De Luca
  • Marta Bogacz
  • Collin Zimmer
  • Annika Wagner
  • Tanja Schirmeister
  • Maria Zappalà
  • Roberta Ettari
DOI
10.3390/ijms232214470
eISSN
1422-0067
Externe Identifier
  • PubMed Identifier: 36430948
  • PubMed Central ID: PMC9698140
Funding acknowledgements
  • University of Messina: FFABR 2020
Open access
true
ISSN
1422-0067
Ausgabe der Veröffentlichung
22
Zeitschrift
International journal of molecular sciences
Schlüsselwörter
  • Humans
  • Trypanosoma brucei rhodesiense
  • Curcumin
  • Nitriles
  • Cysteine Endopeptidases
  • Dipeptides
  • Drug Combinations
  • CD24 Antigen
Sprache
eng
Medium
Electronic
Online publication date
2022
Open access status
Open Access
Paginierung
14470
Datum der Veröffentlichung
2022
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2022
Titel
Drug Combination Studies of the Dipeptide Nitrile CD24 with Curcumin: A New Strategy to Synergistically Inhibit Rhodesain of <i>Trypanosoma brucei rhodesiense</i>.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
23

Files

https://www.mdpi.com/1422-0067/23/22/14470/pdf?version=1669027507 https://europepmc.org/articles/PMC9698140?pdf=render

Data source: Europe PubMed Central

Abstract
Rhodesain is a cysteine protease that is crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite causing the lethal form of Human African Trypanosomiasis. CD24 is a recently developed synthetic inhibitor of rhodesain, characterized by a nanomolar affinity towards the trypanosomal protease (Ki = 16 nM), and acting as a competitive inhibitor. In the present work, we carried out a combination study of CD24 with curcumin, the multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. By applying the Chou and Talalay method, we obtained an initial additive effect at IC50 (fa = 0.5, Combination Index = 1), while for the most relevant fa values, ranging from 0.6 to 1, i.e., from 60% to 100% of rhodesain inhibition, we obtained a combination index < 1, thus suggesting that an increasingly synergistic action occurred for the combination of the synthetic inhibitor CD24 and curcumin. Furthermore, the combination of the two inhibitors showed an antitrypanosomal activity better than that of CD24 alone (EC50 = 4.85 µM and 10.1 µM for the combination and CD24, respectively), thus suggesting the use of the two inhibitors in combination is desirable.
Date of acceptance
2022
Autoren
  • Carla Di Chio
  • Santo Previti
  • Fabiola De Luca
  • Marta Bogacz
  • Collin Zimmer
  • Annika Wagner
  • Tanja Schirmeister
  • Maria Zappalà
  • Roberta Ettari
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/36430948
DOI
10.3390/ijms232214470
eISSN
1422-0067
Externe Identifier
  • PubMed Central ID: PMC9698140
Funding acknowledgements
  • University of Messina: FFABR 2020
Ausgabe der Veröffentlichung
22
Zeitschrift
Int J Mol Sci
Schlüsselwörter
  • combination studies
  • curcumin
  • cysteine protease
  • dipeptide nitrile
  • rhodesain inhibitors
  • Humans
  • Trypanosoma brucei rhodesiense
  • Curcumin
  • Dipeptides
  • Nitriles
  • Cysteine Endopeptidases
  • Drug Combinations
  • CD24 Antigen
Sprache
eng
Country
Switzerland
PII
ijms232214470
Datum der Veröffentlichung
2022
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Drug Combination Studies of the Dipeptide Nitrile CD24 with Curcumin: A New Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
23

Data source: PubMed

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