钌-氯喹配合物对耐药恶性疟原虫的抗疟活性与亲脂性、碱性以及在水/正辛醇界面附近抑制血红素聚集的能力有关。

Martínez Alberto, Rajapakse Chandima S K, Jalloh Dalanda, Dautriche Cula, Sánchez-Delgado Roberto A

Chemistry Department, Brooklyn College, The City University of New York, Brooklyn, NY 11210, USA.

J Biol Inorg Chem. 2009 Aug;14(6):863-71. doi: 10.1007/s00775-009-0498-4. Epub 2009 Apr 3.

We have measured water/n-octanol partition coefficients, pK(a) values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium-pi-arene-chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied.

我们测定了一系列最近报道对恶性疟原虫耐氯喹（CQ）菌株具有活性的钌-π-芳烃-氯喹（CQ）配合物的水/正辛醇分配系数、pK(a)值、血红素结合常数和血红素聚集抑制活性。在水/正辛醇界面附近对金属配合物的血红素聚集抑制活性进行的测量定性地预测了它们相对于CQ对耐药寄生虫具有更强的抗疟作用；我们得出结论，这种改进的方法可能比在酸性水性缓冲液中的标准测试更能预测抗疟效力。我们的数据呈现出一些有趣的趋势，表明抗疟活性与所研究化合物的亲脂性、碱性和结构细节相关的效应平衡有关。