Trypanocidal activity of (−)-cubebin derivatives against free amastigote forms of Trypanosoma cruzi

Souza, Vanessa A. de; Silva, Rosangela da; Pereira, Ana Carolina; Royo, Vanessa de Andrade; Saraiva, Juliana; Montanheiro, Marisa; Souza, Gustavo Henrique Bianco de; Filho, Ademar A. Da Silva; Grando, Marcella Daruge; Donate, Paulo Marcos; Bastos, Jairo Kenupp; Albuquerque, Sérgio de; Silva, Márcio Luís Andrade e

doi:10.1016/j.bmcl.2004.10.079

Cited by 100 publications

(76 citation statements)

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“…Previous studies demonstrated that cubebin and its three presently evaluated derivatives have prominent activity against Trypanosoma cruzi [4,24] and some activity against LLC-MK 2 cell line (unpublished results). The IC 50 values against Trypanosoma cruzi found for (2 )-hinokinin(2), (2 )-9-O-N,N-dimethylamino-ethyl-cubebin(4), (2 )-cubebin(1) and 7-hydroxy-hinokinin(3) were respectively of 0.67, 4.7, 100 and 72 mM, and of respectively 199, 393, 1510 and 1169 mM against LLC-MK 2 cells.…”

Section: Discussionmentioning

confidence: 78%

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Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8

Saraiva

Siqueira

Silva

et al. 2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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The effects on mitochondrial respiration and complex I NADH oxidase activity of cubebin and derivatives were evaluated. The compounds inhibited the state 3 glutamate/malate-supported respiration of hamster liver mitochondria with IC 50 values ranging from 12.16 to 83.96 mM. NADH oxidase reaction was evaluated in submitochondrial particles. The compounds also inhibited this activity, showing the same order of potency observed for effects on state 3 respiration, as well as a tendency towards a non-competitive type of inhibition (K I values ranging from 0.62 to 16.1 mM). A potential binding mode of these compounds with complex I subunit B8, assessed by docking calculations, is proposed.

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Section: Discussionmentioning

confidence: 78%

“…It is a dibenzylbutyrolactone lignan, belonging to a group of compounds with considerable interest as antiviral [2,3], trypanocidal [4], anti-inflammatory [5,6], analgesic [7] and anti-cancer agents [8].…”

Section: Introductionmentioning

confidence: 99%

Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8

Saraiva

Siqueira

Silva

et al. 2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Partial synthesis of (−)-cubebin resulted in (−)-6,6′-Dinitrohinokinin (DNH) and (−)-hinokinin (HQ) which were also tested in T. cruzi parasites and HQ showed to be a potential candidate for the development of a new drug to treat Chagas' disease (Saraiva et al, 2007(Saraiva et al, , 2010. It showed higher trypanocidal activity than benznidazole against epimastigote forms and similar activity against amastigote forms (De Souza et al, 2005;Saraiva et al, 2007). Furthermore, in vivo assays showed significant parasitemic reduction after administration of HQ in mice infected, and it was observed that the groups treated with HQ displayed better survival rates than that treated with benznidazole.…”

Section: Wwwintechopencommentioning

confidence: 99%

Tools for Trans-Splicing Drug Interference Evaluation in Kinetoplastid

Cicarelli¹,

Arnosti²,

Trevelin³

et al. 2012

Parasitology

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“…Em nossos estudos anteriores sobre as lignano lactonas e lactóis várias propriedades biológicas foram relatadas (Saraiva et al, 2007;2009, Silva et al, 2009, Silva et al, 2005Silva et al, 2008;Souza et al, 2005;Silva et al, 2011;Pistolozzi et al, 2013), incluindo a atividade antimicobacteriana (Silva et al, 2009 O extrato etanólico (EE) foi suspenso em solução hidrometanólica (9:1), para cada 20 g de EE foram utilizados aproximadamente 100 mL de solução hidrometanólica. Esta solução foi submetida a partição com hexano (7 x 250 mL), e em seguida separada e concentrada.…”

Section: Introductionunclassified

Avaliação da atividade antimicobacteriana da lignana diidrocubebina extraída da Piper cubeba e de seus derivados semissintéticos

Laurentiz

Borges

Laurentiz

et al. 2015

Rev. bras. plantas med.

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RESUMO:A atividade antimicobacteriana de diidrocubebina (1), uma lignana dibenzilbutanodioica obtida a partir de extrato etanólico de sementes da Piper cubeba, e seus derivados foram avaliados in vitro contra três diferentes cepas de Mycobacterium utilizando o método de microdiluição. Dentre as lignanas avaliadas 3 e 4 foram as mais ativas, exibindo valores de CIM de 62,5 µg/mL contra M. avium e M. tuberculosis, respectivamente. Os derivados 2-6 obtidos por síntese parcial possuem diferentes substituintes nos carbonos 9 e 9 ', que alteram polaridade, solubilidade e limitam as rotações livres entre C8-C8' em relação de material (1) de partida. As diferenças estruturais entre estes compostos podem fornecer informações importantes sobre a relação estrutura-atividade antimicobacteriana do esqueleto dibenzilbutanodioico, obtido a partir de fonte natural, como um possível alvo para o desenvolvimento de drogas mais potentes contra a tuberculose. Palavras-chave: lignanas, diidrocubebina, atividade antimicobacteriana, Piper cubebaABSTRACT: Evaluation of antimycobacterial activity of dihydrocubebin lignan extracted from Piper cubeba and its semisynthetic derivatives. The antimycobacterial activity of the dihydrocubebin (1), a dibenzylbutanedioiclignan obtained from ethanolic extract of Piper cubeba seeds, and its derivatives were examined in vitro against three different strains of Mycobacterium using amicrodilution method. Among the lignans evaluated, the 3 and 4 samples were the most active ones, displaying MIC values of 62.5 μg/mL against M. avium and M. tuberculosis, respectively. The derivatives 2-6, obtained for partial synthesis, had different substituents in the carbons 9 and 9', fact thatalters the polarity, solubility and restricts the free rotations between the bonds C8-C8' in relation to the starting material (1). The structural differences among these compounds provide important information about the antimycobacterial structure-activity relationship of the dibenzylbutanodioic skeleton, obtained from natural source, such as a possible target for the development of more powerful drugs against tuberculosis.

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Trypanocidal activity of (−)-cubebin derivatives against free amastigote forms of Trypanosoma cruzi

Cited by 100 publications

References 15 publications

Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8

Cubebin and derivatives as inhibitors of mitochondrial complex I. Proposed interaction with subunit B8

Tools for Trans-Splicing Drug Interference Evaluation in Kinetoplastid

Avaliação da atividade antimicobacteriana da lignana diidrocubebina extraída da Piper cubeba e de seus derivados semissintéticos

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