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

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%.

SUBMITTER: Ettari R

PROVIDER: S-EPMC7236278 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Ettari Roberta R Previti Santo S Di Chio Carla C Maiorana Santina S Allegra Alessandro A Schirmeister Tanja T Zappalà Maria M

ACS medicinal chemistry letters 20200115 5

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 multitarge ...[more]

PMID: 32435388

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