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

摘要

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 X 10(3) 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 non-competitively with an IC50 of 7.75 mu M. 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%.