{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:58:07Z","timestamp":1791644287595,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rhodesain is a cysteine protease that plays a key role in the life cycle of Trypanosoma brucei rhodesiense, an endemic parasite in sub-Saharan Africa and responsible for Human African Trypanosomiasis (HAT), a disease that can be fatal if not treated promptly. Due to the limitations associated with current HAT pharmacological therapy, the search for new targets for the development of antitrypanosomal agents is urgently needed; in this context, rhodesain represents a promising therapeutic target. In this study, new chalcones were synthesized and tested against rhodesain. Given their affinity for the trypanosomal cysteine protease (Ki values in the micromolar range), chalcone 1a was selected to evaluate its effect in combination with the nutraceutical curcumin. The Combination Index (CI) was calculated using Chou and Talalay\u2019s method. The analysis of the CI calculated at different fa values of enzyme inhibition for the combination curcumin + 1a showed promising results. For all fa values, the CI is less than one, indicating a synergistic effect when chalcone 1a is combined with curcumin. In particular, at the most significant fa value (0.90), corresponding to 90% of enzyme inhibition, the CI value is 0.1781, indicating a strong synergism between the synthetic drug and the nutraceutical. The combined use of curcumin and chalcone 1a led to an enhancement of rhodesain inhibitory activity, resulting in a strong synergistic effect and supporting further investigation of this combination.<\/jats:p>","DOI":"10.3390\/ijms27073320","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:40:31Z","timestamp":1775554831000},"page":"3320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis of New Asymmetrical Chalcones and Evaluation of Their Use in Combination with Curcumin Against Rhodesain of T. brucei rhodesiense"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-3932","authenticated-orcid":false,"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\/0009-0000-9875-7383","authenticated-orcid":false,"given":"Jos\u00e8","family":"Starvaggi","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\/0009-0002-2065-2535","authenticated-orcid":false,"given":"Benito","family":"Natale","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies DiSTABiF, University of Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, 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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3431-9421","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8900-0968","authenticated-orcid":false,"given":"Sandro","family":"Cosconati","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies DiSTABiF, University of Campania Luigi Vanvitelli, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Schirmeister","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Biochemistry, University of Mainz, Staudingerweg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-797X","authenticated-orcid":false,"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":[[2026,4,7]]},"reference":[{"key":"ref_1","unstructured":"(2026, April 01). 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