1448684-75-0Relevant academic research and scientific papers
Ligand-based design, synthesis and biochemical evaluation of potent and selective inhibitors of Schistosoma mansoni dihydroorotate dehydrogenase
Calil, Felipe A.,David, Juliana S.,Chiappetta, Estela R.C.,Fumagalli, Fernando,Mello, Rodrigo B.,Leite, Franco H.A.,Castilho, Marcelo S.,Emery, Flavio S.,Nonato, M.Cristina
, p. 357 - 366 (2019/02/19)
Schistosomiasis ranks second only to malaria as the most common parasitic disease worldwide. 700 million people are at risk and 240 million are already infected. Praziquantel is the anthelmintic of choice but decreasing efficacy has already been documented. In this work, we exploited the inhibition of Schistosoma mansoni dihydroorotate dehydrogenase (SmDHODH) as a strategy to develop new therapeutics to fight schistosomiasis. A series of quinones (atovaquone derivatives and precursors) was evaluated regarding potency and selectivity against both SmDHODH and human DHODH. The best compound identified is 17 (2-hydroxy-3-isopentylnaphthalene-1,4-dione) with IC50 = 23 ± 4 nM and selectivity index of 30.83. Some of the new compounds are useful pharmacological tools and represent new lead structures for further optimization.
In vivo antimalarial activity of novel 2-hydroxy-3-anilino-1,4- naphthoquinones obtained by epoxide ring-opening reaction
Rezende, Lucas Cunha Dias De,Fumagalli, Fernando,Bortolin, Marraiana Schiavon,Oliveira, Marianne Garcia De,Paula, Murilo Helder De,Andrade-Neto, Valter Ferreira De,Emery, Flavio Da Silva
, p. 4583 - 4586 (2013/08/23)
1,4-Naphthoquinone derivatives are known to have relevant activities against several parasites. Among the treatment options for malaria, atovaquone, a 1,4-naphthoquinone derivative, is widely applied in the treatment and prophylaxis of such disease. Based on the structure simplification of atovaquone, we designed and synthesized four novel naphthoquinoidal derivatives. The compounds were obtained by the underexplored epoxide-opening reaction of 1,4-naphthoquinone using aniline derivatives as nucleophiles. The antiplasmodial activity of the synthesized compounds was performed in vivo using Peter's 4 days suppression test. Significant parasitemia reduction and increased survival were observed for some of the compounds.
