Departamento de Química, Instituto de Química, Universidade de São Paulo, São Paulo 05508-000, Brazil.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo 05508-000, Brazil.
Biomolecules. 2022 Apr 26;12(5):638. doi: 10.3390/biom12050638.
Melatonin acts to synchronize the parasite's intraerythrocytic cycle by triggering the phospholipase -inositol 1,4,5-trisphosphate (PLC-IP) signaling cascade. Compounds with an indole scaffold impair in vitro proliferation of blood-stage malaria parasites, indicating that this class of compounds is potentially emerging antiplasmodial drugs. Therefore, we aimed to study the role of the alkyl and aryl thiol moieties of 14 synthetic indole compounds against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of . Four compounds (, , , ) inhibited the growth of (3D7) by 50% at concentrations below 20 µM. A set of 2-sulfenylindoles also showed activity against Dd2 parasites. Our data suggest that Dd2 parasites are more susceptible to compounds and than 3D7 parasites. These data show that 2-sulfenylindoles are promising antimalarials against chloroquine-resistant parasite strains. We also evaluated the effects of the 14 compounds on the parasitemia of the 3D7 strain and their ability to interfere with the effect of 100 nM melatonin on the parasitemia of the 3D7 strain. Our results showed that compounds , , , , , , , and slightly increased the effect of melatonin by increasing parasitemia by 8-20% compared with that of melatonin-only-treated 3D7 parasites. Moreover, we found that melatonin modulates the expression of kinase-related signaling components giving additional evidence to investigate inhibitors that can block melatonin signaling.
褪黑素通过触发磷脂酶-肌醇 1,4,5-三磷酸 (PLC-IP) 信号级联反应来同步寄生虫的红细胞内周期。具有吲哚支架的化合物会损害血期疟原虫的体外增殖，表明这一类化合物可能是新兴的抗疟药物。因此，我们旨在研究 14 种合成吲哚化合物的烷基和芳基硫醇部分对氯喹敏感（3D7）和氯喹抗性（Dd2）株的作用。四种化合物（，，，）在低于 20 μM 的浓度下就能抑制（3D7）的生长，抑制率达到 50%。一组 2-亚磺酰基吲哚也对 Dd2 寄生虫表现出活性。我们的数据表明，Dd2 寄生虫比 3D7 寄生虫更容易受到化合物和的影响。这些数据表明 2-亚磺酰基吲哚是对抗氯喹抗性寄生虫株的有前途的抗疟药物。我们还评估了 14 种化合物对 3D7 株寄生虫血症的影响及其干扰 100 nM 褪黑素对 3D7 株寄生虫血症的影响的能力。我们的结果表明，化合物、、、、、、、和略微增加了褪黑素的效果，使寄生虫血症增加了 8-20%，与仅用褪黑素处理的 3D7 寄生虫相比。此外，我们发现褪黑素调节与激酶相关的信号成分的表达，这为研究可以阻断褪黑素信号的抑制剂提供了额外的证据。
