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Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2018-07-10 , DOI: 10.1016/j.bmc.2018.07.015
Santiago Royo , Tanja Schirmeister , Marcel Kaiser , Sascha Jung , Santiago Rodríguez , José Manuel Bautista , Florenci V. González

A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and even more promising lower values against Leishmania donovanii.



中文翻译:

二肽烯醇酸酯的抗原生动物和半胱氨酸蛋白酶抑制活性

已经制备了二肽烯醇酯家族,并针对与睡眠病,恰加斯病和疟疾有关的寄生性半胱氨酸蛋白酶罗氏蛋白酶,克鲁萨因和falcipain-2进行了测试。还针对人组织蛋白酶B和L1对它们进行了选择性测试。二肽烯醇酸酯是这些酶的不可逆抑制剂。该家族中的某些成员是非常有效的寄生半胱氨酸蛋白酶抑制剂,显示出7个数量级的k 2nd(M -1 s -1)值。还进行了体内抗原生动物测试。抑制剂对恶性疟原虫,布鲁氏锥虫,克鲁氏锥虫的微摩尔范围显示IC 50甚至对利什曼原虫(Leishmania donovanii)的价值更低。

更新日期:2018-07-10
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