Dehydrocrotonin and its β-cyclodextrin complex: Cytotoxicity in V79 fibroblasts and rat cultured hepatocytes

Corrêa, Daniel Henrique do Amaral; Melo, Patrícia S.; Carvalho, Carlos Alberto Alves de; Azevedo, Mariangela de Burgos M de; Durán, Nélson; Haun, Marcela

doi:10.1016/j.ejphar.2005.01.016

Cited by 26 publications

(16 citation statements)

References 25 publications

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“…A atividade citotóxica da DCTN foi estudada em diversas células tumorais das seguintes linhagens: células fi broblásticas pulmonares de hamsters chineses (Souza-Brito et al, 1998;Grynberg et al, 1999;Melo et al, 2001;Rodriguez;Haun, 1999;Freire et al, 2003), células promielocíticas leucêmicas (HL60) (Anazetti et al, 2003;Anazetti et al, 2004;Corrêa et al, 2005), hepatócitos de ratos (Rodriguez; Haun, 1999; Corrêa et al, 2005) (Maciel et al, 2002a;Grynberg et al, 1999;Melo et al, 2004).…”

Section: Citotoxicidade E Atividade Antitumoral: Relação Estrutura-atunclassified

“…A citotoxicidade da DCTN (8 μM), analisada em hepatócitos extraído de ratos, comprovou pelos danos causados nas células hepáticas após tratamento subcrônico da DCTN, a ocorrência de toxicidade seletiva (Rodriguez; Haun, 1999). Outro estudo mostrou a infl uência da DCTN na inibição de fosfatase em células HL60, induzindo apoptose (Corrêa et al, 2005).…”

Section: Citotoxicidade E Atividade Antitumoral: Relação Estrutura-atunclassified

“…No entanto, avanços foram obtidos, tendo sido evidenciada apoptose (Corrêa et al, 2005) e uma possível atividade imunomoduladora pelo aumento de atividade de células NK após tratamento de animais com carcinoma de Ehrlich .…”

Section: Mecanismo De Ação Da Dctnunclassified

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Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

Costa¹,

Magalhães²,

Gomes³

et al. 2007

Rev. bras. farmacogn.

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RESUMO:Croton cajucara Beth (Euphorbiaceae) uma espécie medicinal nativa da região Amazônica do Brasil, onde é vulgarmente conhecida como 'sacaca', representa um recurso terapêutico efi caz no tratamento e cura de várias doenças. O metabólito majoritário transdesidrocrotonina (DCTN), isolado das cascas do caule desta planta, encontra-se correlacionado com grande parte das propriedades medicinais da sacaca. Este artigo de revisão, descreve os resultados fi toquímicos e farmacológicos que foram realizados com o diterpeno do tipo clerodano DCTN, bem como seus derivados semi-sintéticos. Adicionalmente, apresenta perspectivas para a biodisponibilização deste protótipo de fármaco em nanosistemas. Unitermos:Croton cajucara, trans-desidrocrotonina, DCTN, fi toquímica, atividade biológica, nanobiotecnologia.ABSTRACT: "A review of the biologic activities of trans-dehydrocrotonin, a natural product obtained from Croton cajucara". Croton cajucara Beth (Euphorbiaceae) is a plant found in the Amazonian Region of North Brazil, where it is popularly known as sacaca. The major secondary metabolite, trans-dehydrocrotonin (DCTN) a clerodane-type diterpene, isolated from the stem bark is a chief bioactive compound of Croton cajucara. This review describes results of extensive pharmacological studies of DCTN, as well as its semi-synthetic derivatives, and also presents insights into the use of DCTN as a therapeutic agent and some potential advantages of its incorporation in drug delivery systems.

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Section: Citotoxicidade E Atividade Antitumoral: Relação Estrutura-atunclassified

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Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

Costa¹,

Magalhães²,

Gomes³

et al. 2007

Rev. bras. farmacogn.

View full text Add to dashboard Cite

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“…8 The inclusion of the active principles in the cage of β-CD 9,10 protected drugs from absorption in the stomach and the upper portion of the lower intestine and enabled the degradation of the saccharide portion in the large bowel by intestinal microflora, thereby ensuring specific drug delivery with the maximum drug bioavailability. Although investigation into drug inclusion is one of the most extensively researched fields, and complexation and self-assembly of CDs and lipophilic drugs has been investigated for years, [11][12][13] interactions between CDs and hydrophilic drugs have scarcely been reported. [14][15][16] Such an interaction could result in a retarding effect of the associated hydrophilic drug.…”

Section: Introductionmentioning

confidence: 99%

New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

Azevedo¹,

Tasic²,

Fattori³

et al. 2011

IJN

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Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg −1 or 0.09 mg kg −1 , n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL −1 min −1 ) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM) showed a potent and long-lasting inhibitory activity (∼22 hours) on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world’s population who suffer from hypertension.

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“…We also investigated the differences in toxicity between free MTZ-I and its β-CD inclusion complex. It has been well demonstrated that inclusion complexes decrease the toxic effect of some therapeutic agents (Corrêa et al 2005). Furthermore, the complexation of MTZ-I with CD may improve the bioavailability of MTZ-I by enhancing its water solubility.…”

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confidence: 99%

The activity of a metronidazole analogue and its β-cyclodextrin complex against Trypanosoma cruzi

Lopes

Júnior

Lopes

et al. 2011

Mem. Inst. Oswaldo Cruz

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Chagas disease is a potentially life-threatening illness caused by the flagellate protozoan Trypanosoma cruzi. In Brazil, benznidazole is the only drug available for the treatment of Chagas disease, but it has toxic side effects and is only active in the acute phase of the illness (Urbina 1999). With such an unfavourable treatment, the development of new drugs to fight Chagas disease becomes increasingly important.Because nitroaromatics have been found to be active against T. cruzi (Maya et al. 2003), we decided to evaluate the trypanocidal activity of a metronidazole (MTZ) analogue [1-(2-iodoethyl)-2-methyl-5-nitroimidazole (MTZ-I)] (Fig. 1) previously synthesised in our laboratory (Busatti et al. 2007) and its beta-cyclodextrin (β-CD) inclusion complex. We also investigated the differences in toxicity between free MTZ-I and its β-CD inclusion complex. It has been well demonstrated that inclusion complexes decrease the toxic effect of some therapeutic agents (Corrêa et al. 2005). Furthermore, the complexation of MTZ-I with CD may improve the bioavailability of MTZ-I by enhancing its water solubility.The solubility of the complex was evaluated in relation to MTZ-I with a phase solubility study. The phase solubility diagram of MTZ-I and β-CD was obtained by plotting the changes in guest solubility as a function of β-CD concentration. The solubility curve can be classified as a B s curve according to Higuchi and Connors (1965). The complex exhibits higher solubility than the guest molecule, but its limit was reached within the CD concentration ranges that were tested. Increasing the amount of available CD-molecules did not lead to a rise in solubility. However, the MTZ-I solubility increased considerably with an equimolar ratio of MTZ-I:β-CD.The solid-state inclusion complex was characterised using infrared (IR) spectroscopy and differential scanning calorimetry (DSC). A comparison between the IR spectra of MTZ-I, β-CD, MTZ-I and β-CD in a simple 1:1 physical mixture (PM) and MTZ-I and β-CD as a complex shows some significant changes in the shape and position of the absorbance bands of the MTZ-I functional groups. Analysis of the IR spectra of the inclusion complexes revealed the most frequent changes to be in the range of 700-660 cm -1 , which were interpreted as the band corresponding to the vibration of the C-I bond. Differences were also found in the 1,526 and 1,356 cm -1 regions, which were attributed to the skeleton vibrations of the C-NO 2 group. Less pronounced changes were observed in the IR spectrum of the PM. The DSC thermal behaviours of MTZ-I, β-CD, the MTZ-I:β-CD complex and the MTZ-I:β-CD PM were also studied. The DSC curve for MTZ-I showed a typical pure crystalline substance profile with a sharp endothermic peak at 101.2ºC. The DSC curve of β-CD showed a broad endothermic peak in the range of 75-85ºC, which can be attributed to desolvation, followed by a small endothermic peak at 220.16ºC. The formation of an inclusion complex was suggested by the absence of a melting endothermic peak for MTZ-I in...

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Dehydrocrotonin and its β-cyclodextrin complex: Cytotoxicity in V79 fibroblasts and rat cultured hepatocytes

Cited by 26 publications

References 25 publications

Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

The activity of a metronidazole analogue and its β-cyclodextrin complex against Trypanosoma cruzi

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