Drug Synergism: Studies of Combination of RK-52 and Curcumin against Rhodesain of Trypanosoma brucei rhodesiense.,ACS Medicinal Chemistry Letters

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Drug Synergism: Studies of Combination of RK-52 and Curcumin against Rhodesain of Trypanosoma brucei rhodesiense.
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-01-15 , DOI: 10.1021/acsmedchemlett.9b00635
Roberta Ettari ₁ , Santo Previti ₁ , Carla Di Chio ₁ , Santina Maiorana ₁ , Alessandro Allegra ₂ , Tanja Schirmeister ₃ , Maria Zappalà ₁

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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 fa values, which means a potent synergistic effect for the reduction of rhodesain activity from 40% to 99%.

中文翻译：

药物协同作用：RK-52和姜黄素联合治疗布氏锥虫的罗得沙氏菌的研究。

罗德赛因是布鲁氏罗氏锥虫生活中必不可少的一种酶，这种寄生虫会引起人类非洲锥虫病的快速发作。RK-52是罗德沙因的合成抑制剂，其特征在于令人印象深刻的k秒值（k秒= 67000×103 M-1 min-1）和对锥虫蛋白酶的皮摩尔亲和力（K i = 38 pM）。与此不同的是，姜黄素是一种从姜黄获得的金色多靶标营养品，经证实可非竞争性地抑制罗得沙星，IC50为7.75μM。在本研究中，我们通过应用Chou和Talalay方法对RK-52和姜黄素联合用于罗得沙因进行了研究，这使我们获得了最相关fa值的组合指数<1，这意味着罗丹素活性从40％降低到99％的协同作用。

更新日期：2020-01-15

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