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Projeto de investigação
A small couple against the big three
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Drug‐derived surface‐active ionic liquids: a cost‐effective way to expressively increase the blood‐stage antimalarial activity of Primaquine
Publication . Silva, Ana Teresa; Oliveira, Isabel S.; Gomes, Joana; Aguiar, Luísa; Fontinha, Diana; Duarte, Denise; Nogueira, Fátima; Prudêncio, Miguel; Marques, Eduardo F.; Teixeira, Cátia; Ferraz, Ricardo; Gomes, Paula
Inspired by previous disclosure of room-temperature ionic liquids derived from primaquine and cinnamic acids, which displayed slightly enhanced blood-stage activity compared to the parent drug, we have now combined this emblematic antimalarial with natural fatty acids. This affords surface-active ionic liquids whose liver-stage antiplasmodial activity is either retained or slightly enhanced, while revealing blood-stage antiplasmodial activity at least one order of magnitude higher than that of the parent compound. These findings open new perspectives towards the cost-effective recycling of classical drugs that are either shelved or in decline, and which is not limited to antimalarial agents.
4,9‐Diaminoacridines and 4‐Aminoacridines as dual‐stage antiplasmodial hits
Publication . Fonte, Mélanie; Tassi, Natália; Fontinha, Diana; Bouzón‐Arnáiz, Inés; Ferraz, Ricardo; Araújo, Maria J.; Fernàndez‐Busquets, Xavier; Prudêncio, Miguel; Gomes, Paula; Teixeira, Cátia
Multi-stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine-based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine-sensitive and -resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual-stage antiplasmodial hits.
Cinnamic acid conjugates in the rescuing and repurposing of classical antimalarial drugs
Publication . Silva, Ana Teresa; Bento, Clara M.; Pena, Ana C; Figueiredo, Luisa M.; Prudêncio, Cristina; Aguiar, Luísa; Silva, Tânia; Ferraz, Ricardo; Gomes, Maria Salomé; Teixeira, Cátia; Gomes, Paula
Cinnamic acids are compounds of natural origin that can be found in many different parts of a wide panoply of plants, where they play the most diverse biological roles, often in a conjugated form. For a long time, this has been driving Medicinal Chemists towards the investigation of the therapeutic potential of natural, semi-synthetic, or fully synthetic cinnamic acid conjugates. These efforts have been steadily disclosing promising drug leads, but a wide chemical space remains that deserves to be further explored. Amongst different reported approaches, the combination or conjugation of cinnamic acids with known drugs has been addressed in an attempt to produce either synergistic or multi-target action. In this connection, the present review will focus on efforts of the past decade regarding conjugation with cinnamic acids as a tool for the rescuing or the repurposing of classical antimalarial drugs, and also on future perspectives in this particular field of research.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
3599-PPCDT
Número da atribuição
PTDC/BTM-SAL/29786/2017