{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:33:54Z","timestamp":1791920034630,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008908","name":"University of Messina","doi-asserted-by":"publisher","award":["FFABR 2020"],"award-info":[{"award-number":["FFABR 2020"]}],"id":[{"id":"10.13039\/501100008908","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"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 \u00b5M and 10.1 \u00b5M for the combination and CD24, respectively), thus suggesting the use of the two inhibitors in combination is desirable.<\/jats:p>","DOI":"10.3390\/ijms232214470","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T02:59:22Z","timestamp":1669085962000},"page":"14470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Drug Combination Studies of the Dipeptide Nitrile CD24 with Curcumin: A New Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense"],"prefix":"10.3390","volume":"23","author":[{"given":"Carla","family":"Di Chio","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-3321","authenticated-orcid":false,"given":"Santo","family":"Previti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bogacz","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry & Macromolecular Chemistry, Friedrich-Schiller University of Jena, Humboldtstra\u00dfe 10, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudingerweg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry & Macromolecular Chemistry, Friedrich-Schiller University of Jena, Humboldtstra\u00dfe 10, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Schirmeister","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudingerweg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zappal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-2068","authenticated-orcid":false,"given":"Roberta","family":"Ettari","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, September 04). 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