Drug Synergism: Studies of Combination of RK-52 and Curcumin against Rhodesain of Trypanosoma brucei rhodesiense

Roberta Ettari; Santo Previti; Carla Di Chio; Santina Maiorana; Alessandro Allegra; Tanja Schirmeister; Maria Zappalà

doi:10.1021/acsmedchemlett.9b00635

Drug Synergism: Studies of Combination of RK-52 and Curcumin against Rhodesain of Trypanosoma brucei rhodesiense

ACS Med Chem Lett. 2020 Jan 15;11(5):806-810. doi: 10.1021/acsmedchemlett.9b00635. eCollection 2020 May 14.

Authors

Roberta Ettari¹, Santo Previti¹, Carla Di Chio¹, Santina Maiorana¹, Alessandro Allegra², Tanja Schirmeister³, Maria Zappalà¹

Affiliations

¹ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy.
² Division of Hematology, Department of General Surgery, Pathological Anatomy and Oncology, University of Messina, Via Consolare Valeria, 90100 Messina, Italy.
³ Institute of Pharmacy and Biochemistry, University of Mainz, Johann-Joachim-Becherweg 30, DE 55128 Mainz, Germany.

Abstract

Rhodesain is an enzyme essential for the life of Trypanosoma brucei rhodesiense, a parasite causing a rapid-onset form of Human African Trypanosomiasis. RK-52 is a synthetic inhibitor of rhodesain, characterized by an impressive k _second value (k _second = 67000 × 10³ M^-1 min^-1) and by a picomolar affinity toward the trypanosomal protease (K _i = 38 pM). Differently, curcumin, the golden multitarget nutraceutical obtained from Curcuma longa L., was proven to inhibit rhodesain noncompetitively with an IC₅₀ of 7.75 μM. In the present study, we carried out studies of a combination of RK-52 and curcumin toward rhodesain, by applying the Chou and Talalay approach, which led us to obtain a combination index <1 for the most relevant f_a values, which means a potent synergistic effect for the reduction of rhodesain activity from 40% to 99%.