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

Abstract

Rhodesain is an enzyme essential for the life of <i>Trypanosoma brucei rhodesiense,</i> a parasite causing a rapid-onset form of Human African Trypanosomiasis. <b>RK-52</b> is a synthetic inhibitor of rhodesain, characterized by an impressive <i>k</i> _second value (<i>k</i> _second = 67000 × 10³ M^-1 min^-1) and by a picomolar affinity toward the trypanosomal protease (<i>K</i> _i = 38 pM). Differently, curcumin, the golden multitarget nutraceutical obtained from <i>Curcuma longa</i> 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%.