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Drug Synergism: Studies of Combination of RK-52 and Curcumin against Rhodesain of Trypanosoma brucei rhodesiense
journal contribution
posted on 2020-01-17, 18:03 authored by Roberta Ettari, Santo Previti, Carla Di Chio, Santina Maiorana, Alessandro Allegra, Tanja Schirmeister, Maria ZappalàRhodesain 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 ksecond value (ksecond = 67000
× 103 M–1 min–1) and by a picomolar affinity toward the trypanosomal protease (Ki = 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 fa values, which means
a potent synergistic effect for the reduction of rhodesain activity
from 40% to 99%.