Domínguez J N, López S, Charris J, Iarruso L, Lobo G, Semenov A, Olson J E, Rosenthal P J
Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela.
J Med Chem. 1997 Aug 15;40(17):2726-32. doi: 10.1021/jm970266p.
Acridinediones have previously been shown to have potent antimalarial activity. A series of sulfur isosteres of acridinediones have been synthesized and evaluated for their inhibition of the Plasmodium falciparum cysteine protease falcipain and for their antimalarial activity. A number of these phenothiazines inhibited falcipain and demonstrated activity against cultured P. falciparum parasites at low micromolar concentrations. We propose that the compounds exerted their antimalarial effects by two mechanisms, one of which involves the inhibition of falcipain and a consequent block in parasite degradation of hemoglobin. These compounds and related phenothiazines are worthy of further study as potential antimalarial agents.
吖啶二酮先前已被证明具有强大的抗疟活性。已合成了一系列吖啶二酮的硫代电子等排体，并对其抑制恶性疟原虫半胱氨酸蛋白酶疟原虫蛋白酶以及抗疟活性进行了评估。其中许多吩噻嗪抑制疟原虫蛋白酶，并在低微摩尔浓度下对培养的恶性疟原虫寄生虫表现出活性。我们认为这些化合物通过两种机制发挥抗疟作用，其中一种机制涉及抑制疟原虫蛋白酶并进而阻断寄生虫对血红蛋白的降解。这些化合物及相关吩噻嗪作为潜在抗疟药物值得进一步研究。
