Silva Ana Teresa, Oliveira Isabel, Duarte Denise, Moita Diana, Prudêncio Miguel, Nogueira Fátima, Ferraz Ricardo, Marques Eduardo Figueira, Gomes Paula
LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto P-4169-007 Porto Portugal
CIQUP - IMS, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto P-4169-007 Porto Portugal.
RSC Med Chem. 2024 May 10;15(8):2657-2662. doi: 10.1039/d4md00007b. eCollection 2024 Aug 14.
Malaria is one of the "big three" global infectious diseases, having caused above two hundred million cases and over half a million deaths in 2020. The continuous demand for new treatment options prioritizes the cost-effective development of new chemical entities with multi-stage antiplasmodial activity, for higher efficacy and lower propensity to elicit drug-resistant parasite strains. Following up on our long-term research towards the rescue of classical antimalarial aminoquinolines like chloroquine and primaquine, we have developed new organic salts by acid-base pairing of those drugs with natural bile acids. These antimalarial drug-derived bile salts were screened against the hepatic, blood and gametocyte stages of parasites, unveiling chloroquine bile salts as unprecedented triple-stage antiplasmodial hits. These findings pave a new pathway for drug rescuing, even beyond anti-malarial and other anti-infective drugs.
疟疾是全球“三大”传染病之一,2020年已导致超过2亿例病例和50多万人死亡。对新治疗方案的持续需求使得开发具有多阶段抗疟原虫活性的新化学实体成为优先事项,以实现更高的疗效并降低引发耐药寄生虫菌株的可能性。在我们长期致力于拯救氯喹和伯氨喹等经典抗疟氨基喹啉的研究基础上,我们通过将这些药物与天然胆汁酸进行酸碱配对,开发出了新的有机盐。这些抗疟药物衍生的胆汁盐针对寄生虫的肝脏、血液和配子体阶段进行了筛选,发现氯喹胆汁盐是前所未有的三阶段抗疟原虫活性物质。这些发现为药物拯救开辟了一条新途径,甚至超越了抗疟疾和其他抗感染药物。
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