Activities of naphthoquinones against Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae), vector of dengue and Biomphalaria glabrata (Say, 1818), intermediate host of Schistosoma mansoni

Larvicidal (against Aedes aegypti Linnaeus, 1762) and molluscicidal (against Biomphalaria glabrata Say,1818) activities of several natural and synthetic naphthoquinoneswere measured, with significant results. The best larvicidal compound is 3-bromojuglone, while the better molluscicides are 2-bromo- and 3- bromo-5-acetoxy-1,4-naphthoquinones together with the 3-bromo-5-methoxy derivative. The present results reinforce the potential use of substituted hydroxyquinones, their salts and halogenated quinones as very promising compounds against 4th instar larves of Aedes aegypti, the vector of dengue and against adult snail of Biomphalaria glabrata.This work was supported by CNPq, RHAE/CNPq, Ministério da Saúde/Programa Dengue, CAPES and FAPEAL (Fundac¸ ão de Apoio à Pesquisa do Estado de Alagoas, Maceió, Al. Brazil), IMSEAR, BNB, RENORBIO, IM-INOFAR/CNPq, CSIC-CNPq (2005 BR0046, to M.T.M and M.O.F.G), DGICYT ((Spain, grants BQU2003- 00813 and SAF2006-04698 to M.T.M.), CSIC (for a I3P contract to E.L.-M.)Peer reviewe

Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent

Submitted by Éder Freyre ([email protected]) on 2017-02-13T13:10:12Z No. of bitstreams: 1 ve_Diogo_Moreira_etal_CPqGM_2014.pdf: 1053015 bytes, checksum: 283a95300677183e0f6d3a26fe6a040c (MD5)Approved for entry into archive by Éder Freyre ([email protected]) on 2017-02-13T16:20:17Z (GMT) No. of bitstreams: 1 ve_Diogo_Moreira_etal_CPqGM_2014.pdf: 1053015 bytes, checksum: 283a95300677183e0f6d3a26fe6a040c (MD5)Made available in DSpace on 2017-02-13T16:20:17Z (GMT). No. of bitstreams: 1 ve_Diogo_Moreira_etal_CPqGM_2014.pdf: 1053015 bytes, checksum: 283a95300677183e0f6d3a26fe6a040c (MD5) Previous issue date: 2015CNPq, FAPESB, FAPEAL e CAPES.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade Federal Rural de Pernambuco. Departamento de Química. Recife, PE, Brasil.Universidade Federal Rural de Pernambuco. Departamento de Química. Recife, PE, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the β-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol