7 documents found, page 1 of 1
Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative ef...
Fonte, Mélanie; Rôla, Catarina; Santana, Sofia; Ferraz, Ricardo; Prudêncio, Miguel; Almeida, Joana; Ferraz, Ricardo; Prudêncio, CristinaDrug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compound...
New 4-(N-cinnamoylbutyl)aminoacridines as potential multi-stage antiplasmodial ...
Fonte, Mélanie; Fontinha, Diana; Moita, Diana; Caño-Prades, Omar; Avalos-Padilla, Yunuen; Fernàndez-Busquets, Xavier; Prudêncio, Miguel; Gomes, PaulaA novel family of 4-aminoacridine derivatives was obtained by linking this heteroaromatic core to different trans-cinnamic acids. The 4-(N-cinnamoylbutyl)aminoacridines obtained exhibited in vitro activity in the low- or sub-micromolar range against (i) hepatic stages of Plasmodium berghei, (ii) erythrocytic forms of Plasmodium falciparum, and (iii) early and mature gametocytes of Plasmodium falciparum. The mos...
New 4-aminoacridine-cinnamic acid conjugates as multi-stage antimalarial hits
Fonte, Mélanie; Fontinha, Diana; Moita, Diana; Prades, Omar; Padilla, Yunuen; Ferraz, Ricardo; Fernàndez-Busquets, Xavier; Prudêncio, MiguelThe eradication of malaria remains to be achieved, mainly due to the continued spread of drugresistant parasites. To overcome this, multi-stage drugs have been prioritized in antimalarial drug discovery, since targeting more than one process in the Plasmodium’s life cycle may increase efficiency, while decreasing the chances of resistance emergence by the parasite. Quinacrine (QN) was the first synthetic antipl...
4,9-Diaminoacridines and 4-Aminoacridines as Dual-Stage Antiplasmodial Hits
Fonte, Mélanie; Tassi, Natália; Fontinha, Diana; Bóuzon-Arnáiz, Inês; Ferraz, Ricardo; Araújo, Maria J.; Fèrnandez-Busquets, Xavier; Prudêncio, MiguelMulti‐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 ...
4,9‐Diaminoacridines and 4‐Aminoacridines as dual‐stage antiplasmodial hits
Fonte, Mélanie; Tassi, Natália; Fontinha, Diana; Bouzón‐Arnáiz, Inés; Ferraz, Ricardo; Araújo, Maria J.; Fernàndez‐Busquets, Xavier; Prudêncio, MiguelMulti-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 ...
Development of a synthetic route towards N4 ,N9 -disubstituted 4,9-diaminoacrid...
Fonte, Mélanie; Fagundes, Natália; Gomes, Ana; Ferraz, Ricardo; Prudêncio, Cristina; Araújo, Maria João; Gomes, Paula; Teixeira, CátiaMalaria is one of the deadliest infectious diseases in the world and was responsible for 435 000 deaths in 2017, namely by Plasmodium falciparum species.1 Antimalarial drugs are the unique weapon to fight this disease once there is no vaccine yet. Generally antimalarial chemotherapy targets mainly the pathogenic blood stage in humans. However, there is an urgent need of new, economic and safe drugs in order to:...
Development of a synthetic route towards N4,N9-disubstituted 4,9-diaminoacridin...
Fonte, Mélanie; Fagundes, Natália; Gomes, Ana; Ferraz, Ricardo; Prudêncio, Cristina; Araújo, Maria João; Gomes, Paula; Teixeira, CátiaA multi-step synthetic route towards N4,N9-disubstituted 4,9-diaminoacridines that, to the best of our knowledge, has no precedence in the literature, has been developed. The target structures are likely to reveal interesting biological activities in the near future, not only due to their mepacrine-like core, but also because they embed simultaneously the pharmacophores of chloroquine and primaquine, antimalari...