Pradines Bruno, Alibert Sandrine, Houdoin Carole, Santelli-Rouvier Christiane, Mosnier Joel, Fusai Thierry, Rogier Christophe, Barbe Jacques, Parzy Daniel
Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France.
Antimicrob Agents Chemother. 2002 Jul;46(7):2061-8. doi: 10.1128/AAC.46.7.2061-2068.2002.
The effects of a series of dihydroethano- and ethenoanthracene derivatives on chloroquine (CQ) accumulation in CQ-susceptible strain 3D7 and CQ-resistant clone W2 were assessed. The levels of CQ accumulation increased little or none in CQ-susceptible strain 3D7 and generally increased markedly in CQ-resistant strain W2. At 10 microM, 28 compounds yielded cellular accumulation ratios (CARs) greater than that observed with CQ alone in W2. At 10 microM, in strain W2, 21 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 15 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 13 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 9 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 microM, 17 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 12 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 6 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 3 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 microM, 17 of 31 compounds were more potent inducers of CQ accumulation than verapamil and 12 of 31 compounds were more potent inducers of CQ accumulation than promethazine. The nature of the basic group seems to be associated with increases in the levels of CQ accumulation. At 1 and 10 microM, 10 of 14 and 13 of 14 compounds with amino group (amines and diamines), respectively, had CARs >or=3, while at 1 and 10 microM, only 1 of the 13 derivatives with amido groups had CARs >or=3. Among 12 of the 31 compounds which were more active inducers of CQ accumulation than promethazine at 1 microM, 10 had amino groups and 1 had an amido group.
评估了一系列二氢乙烷和乙烯蒽衍生物对氯喹（CQ）在氯喹敏感株3D7和氯喹抗性克隆W2中蓄积的影响。在氯喹敏感株3D7中，CQ蓄积水平几乎没有增加或没有增加，而在氯喹抗性株W2中通常显著增加。在10微摩尔浓度下，28种化合物产生的细胞蓄积率（CARs）高于单独使用CQ在W2中观察到的水平。在10微摩尔浓度下，在W2株中，31种化合物中有21种的CQ CARs比单独使用CQ高两倍或更多倍，31种化合物中有15种的CQ CARs比单独使用CQ高三倍或更多倍，31种化合物中有13种的CQ CARs比单独使用CQ高四倍或更多倍，31种化合物中有9种的CQ CARs比单独使用CQ高五倍或更多倍。在1微摩尔浓度下，31种化合物中有17种的CQ CARs比单独使用CQ高两倍或更多倍，31种化合物中有12种的CQ CARs比单独使用CQ高三倍或更多倍，31种化合物中有6种的CQ CARs比单独使用CQ高四倍或更多倍，31种化合物中有3种的CQ CARs比单独使用CQ高五倍或更多倍。在1微摩尔浓度下，31种化合物中有17种是比维拉帕米更强的CQ蓄积诱导剂，31种化合物中有12种是比异丙嗪更强的CQ蓄积诱导剂。碱性基团的性质似乎与CQ蓄积水平的增加有关。在1和10微摩尔浓度下，分别有14种含氨基（胺类和二胺类）的化合物中的10种和13种的CARs≥3，而在1和10微摩尔浓度下，13种含酰胺基的衍生物中只有1种的CARs≥3。在1微摩尔浓度下比异丙嗪更具活性的CQ蓄积诱导剂的31种化合物中的12种中，10种含有氨基，1种含有酰胺基。
