Background: Malaria represents the major parasitic disease in tropical regions, and the development of new potent drugs is of pivotal importance. In this study, a series of hybrid molecules were designed by linking the 7-chloroquinoline core of chloroquine to different fluorinated flavonoid-related scaffolds. Materials & methods: Compounds were prepared by exploiting the click chemistry approach, allowing the introduction of a 1,2,3-triazole, a privileged structural motif in antiparasitic dug discovery. Results: Compounds 1b and 1c were the most interesting and were endowed with the highest in vitro activity, mainly against a resistant Plasmodium falciparum strain. They also inhibited hemozoin formation, and 1c was more effective than chloroquine against stage V gametocytes. Conclusion: The homoisoflavone core is a new, promising antimalarial scaffold that deserves further investigation.

Hitting drug-resistant malaria infection with triazole-linked flavonoid–chloroquine hybrid compounds

Seghetti, Francesca
Primo
;
Belluti, Federica;Rampa, Angela;Gobbi, Silvia;Bisi, Alessandra
Ultimo
2022

Abstract

Background: Malaria represents the major parasitic disease in tropical regions, and the development of new potent drugs is of pivotal importance. In this study, a series of hybrid molecules were designed by linking the 7-chloroquinoline core of chloroquine to different fluorinated flavonoid-related scaffolds. Materials & methods: Compounds were prepared by exploiting the click chemistry approach, allowing the introduction of a 1,2,3-triazole, a privileged structural motif in antiparasitic dug discovery. Results: Compounds 1b and 1c were the most interesting and were endowed with the highest in vitro activity, mainly against a resistant Plasmodium falciparum strain. They also inhibited hemozoin formation, and 1c was more effective than chloroquine against stage V gametocytes. Conclusion: The homoisoflavone core is a new, promising antimalarial scaffold that deserves further investigation.
2022
Seghetti, Francesca; Belluti, Federica; Rampa, Angela; Gobbi, Silvia; Legac, Jenny; Parapini, Silvia; Basilico, Nicoletta; Bisi, Alessandra
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/913984
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