TY - JOUR
T1 - “Seasoning” antimalarial drugs' action
T2 - chloroquine bile salts as novel triple-stage antiplasmodial hits
AU - Silva, Ana Teresa
AU - Oliveira, Isabel
AU - Duarte, Denise
AU - Moita, Diana
AU - Prudêncio, Miguel
AU - Nogueira, Fátima
AU - Ferraz, Ricardo
AU - Marques, Eduardo Figueira
AU - Gomes, Paula
N1 - Funding Information:
This work received funding from the PT national funds (Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia/Minist\u00E9rio da Ci\u00EAncia, Tecnologia e Ensino Superior \u2013 FCT/MCTES) through the project CIRCNA/BRB/0281/2019. FCT/MCTES is further acknowledged for supporting the Research Units LAQV-REQUIMTE (UIDB/50006/2020 and UIDP/50006/2020), CIQ-UP (UIDB/00081/2020), and GHTM (UID/Multi/04413/2013). ATS thanks both FCT/MCTES and Sociedade Portuguesa de Qu\u00EDmica (SPQ, Portugal) for her doctoral grant SFRH/BD/150649/2020.
Publisher Copyright:
© 2024 RSC.
PY - 2024/8/14
Y1 - 2024/8/14
N2 - 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 in vitro against the hepatic, blood and gametocyte stages of Plasmodium 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.
AB - 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 in vitro against the hepatic, blood and gametocyte stages of Plasmodium 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.
UR - http://www.scopus.com/inward/record.url?scp=85194160746&partnerID=8YFLogxK
U2 - 10.1039/d4md00007b
DO - 10.1039/d4md00007b
M3 - Article
C2 - 39149112
AN - SCOPUS:85194160746
SN - 2632-8682
VL - 15
SP - 2657
EP - 2662
JO - RSC Medicinal Chemistry
JF - RSC Medicinal Chemistry
IS - 8
ER -