Journal Article

Synthesis of New Asymmetrical Chalcones and Evaluation of Their Use in Combination with Curcumin Against Rhodesain of T. brucei rhodesiense

Schirmeister, Tanja, Zappalà, Maria, Di Chio, Carla, De Luca, Fabiola, Ettari, Roberta, Starvaggi, Josè, Cosconati, Sandro, Natale, Benito, Previti, Santo

2026

Overview

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’s 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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Chalcones - chemical synthesis / Chalcones - chemistry / Chalcones - pharmacology / Curcumin - chemistry / Curcumin - pharmacology / Cysteine / Cysteine Endopeptidases - chemistry / Cysteine Endopeptidases - metabolism / Cysteine Proteinase Inhibitors - chemical synthesis / Cysteine Proteinase Inhibitors - chemistry / Cysteine Proteinase Inhibitors - pharmacology / Drug Synergism / Enzymes / Functional foods / Health aspects / Humans / Parasites / Patient compliance / Pentamidine isethionate / Proteases / Suramin sodium / Tropical diseases / Trypanocidal Agents - chemical synthesis / Trypanocidal Agents - chemistry / Trypanocidal Agents - pharmacology / Trypanosoma brucei rhodesiense - drug effects / Trypanosoma brucei rhodesiense - enzymology