Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies
Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2014-08-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762014000500546&lng=en&tlng=en |
| _version_ | 1827833164925501440 |
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| author | Nicolli Bellotti de Souza Isabel M de Andrade Paula F Carneiro Guilherme AM Jardim Isadora MM de Melo Eufrânio N da Silva Júnior Antoniana Ursine Krettli |
| author_facet | Nicolli Bellotti de Souza Isabel M de Andrade Paula F Carneiro Guilherme AM Jardim Isadora MM de Melo Eufrânio N da Silva Júnior Antoniana Ursine Krettli |
| author_sort | Nicolli Bellotti de Souza |
| collection | DOAJ |
| description | Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study. |
| first_indexed | 2024-03-12T05:25:53Z |
| format | Article |
| id | doaj.art-7e79382be4df4a7b99506fa9cedfd536 |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T05:25:53Z |
| publishDate | 2014-08-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-7e79382be4df4a7b99506fa9cedfd5362023-09-03T07:24:31ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-80602014-08-01109554655210.1590/0074-0276130603S0074-02762014000500546Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studiesNicolli Bellotti de SouzaIsabel M de AndradePaula F CarneiroGuilherme AM JardimIsadora MM de MeloEufrânio N da Silva JúniorAntoniana Ursine KrettliDue to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762014000500546&lng=en&tlng=enantimalarialsquinonesphenazineslapacholPlasmodium falciparumPlasmodium berghei |
| spellingShingle | Nicolli Bellotti de Souza Isabel M de Andrade Paula F Carneiro Guilherme AM Jardim Isadora MM de Melo Eufrânio N da Silva Júnior Antoniana Ursine Krettli Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies Memorias do Instituto Oswaldo Cruz antimalarials quinones phenazines lapachol Plasmodium falciparum Plasmodium berghei |
| title | Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies |
| title_full | Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies |
| title_fullStr | Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies |
| title_full_unstemmed | Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies |
| title_short | Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies |
| title_sort | blood shizonticidal activities of phenazines and naphthoquinoidal compounds against plasmodium falciparum in vitro and in mice malaria studies |
| topic | antimalarials quinones phenazines lapachol Plasmodium falciparum Plasmodium berghei |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762014000500546&lng=en&tlng=en |
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