Lunacridine from Lunasia amara is a DNA intercalating topoisomerase II inhibitor

Prescott, Thomas A.K.; Sadler, Ian H.; Kiapranis, Robert; Maciver, Sutherland K.

doi:10.1016/j.jep.2006.07.036

Cited by 42 publications

(24 citation statements)

References 16 publications

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“…Oral application by drinking the alcohol-tinctured preparation is for treatment of stomach troubles, poisoning, ulcer, nausea, diarrhea, gastroenteritis or as an antitoxin, antibacterial and antiviral treatment. The information generated from the key informants shows similarities of other reported traditional use of Lunasia amara Blanco in the treatment of various health issues ranging from treatment of a variety of health issues and conditions ranging from snake bites, stomach troubles and diarrhea 20 , gastralgia and adynamic conditions of digestive system 32 , infected eyes, swollen limbs and skin diseases 33 , tuberculosis 15 , tropical ulcers 21 , bacterial infections and diseases 24 & infertility 34,35 .…”

Section: In-vitro Mtt Assay Of Splenocyte Proliferationmentioning

confidence: 84%

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2018

IJPSR

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ABSTRACT:This study was conducted to evaluate the antimicrobial and cellular metabolic inhibitory properties of the ethanolic extract from the bark of 'Lunas-bagon', Lunasia sp. Extracts were evaluated using the agar well diffusion method for antimicrobial assay. The standard phytochemical screening was done for the determination of compounds that can be considered toxic and MTT assay for the effects of the extract on cellular metabolism. Results showed that the extracts have ability to inhibit selected Gram-positive and Gram-negative bacterial isolates indicating that the extracts are effective antibacterials. Results from the MTT assay revealed at doses lower than 100.0 ug/ml, extracts will not inhibit cellular metabolism of the splenocytes. Higher dose, however shows reduction of metabolic activity which may indicate the onset of apoptosis in cells. Basic biochemical tests indicated the absence of cyanogenic glycosides and anthraquinones, thus the extracts may not have toxic effects. Identification of bioactive compounds in through GC-MS analysis showed the presence of compounds that are known as antimicrobials and also effective in the treatment of selected healthrelated problems and conditions. The information generated in this study clearly indicates that the folk medical uses of 'Lunas-bagon', Lunasia sp. have antimicrobial and biochemical bases.

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Section: In-vitro Mtt Assay Of Splenocyte Proliferationmentioning

confidence: 84%

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2018

IJPSR

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“…Na tentativa de descobrir novos inibidores da topoisomerase, diversas classes de produtos naturais têm sido testadas e descritas na literatura nos últimos anos. Dentre estas classes, podemos citar os fl avonóides (Constantinou et al, 1995;Shi et al, 1995) e bifl avonóides (Grynberg et al, 2002), diterpenos (Maciel et al, 2007) e triterpenóides (Wada et al, 1998), estilbenóides (Yamada et al, 2006), alcalóides (Woo et al, 1997;Prescott et al, 2007), naftodiantronas (Peebles et al, 2001), naftoquinonas (Ting et al, 2003;Phyta et al, 1998;Esteves-Souza et al, 2007) e binaftoquinonas (Cunha et al, 2006), derivados do núcleo cromano (Ishar et al, 2006), entre outras.…”

Section: Introductionunclassified

Rubrofusarina, um policetídeo natural inibidor da topoisomerase II-α humana

Branco¹,

Pinto²,

Braz‐Filho³

et al. 2008

Rev. bras. farmacogn.

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RESUMO:Este trabalho descreve o efeito inibitório de rubrofusarina (5,6-diidroxi-8-metoxi-2-metilbenzo[g]cromen-4-ona, 1) sobre a enzima DNA topoisomerase II-humana. Rubrofusarina mostrou total inibição da enzima topisomerase II-na concentração de 120 M. Este resultado é semelhante ao observado com etoposida, utilizada como controle positivo. Para a realização deste teste, rubrofusarina foi isolada de Senna macranthera var. nervosa (Voguel) Irwin & Barnebyem e caracterizada por métodos espectroscópicos, incluindo RMN 2D, do produto natural bem como de seu derivado monoacetilado.Unitermos: Rubrofusasina, topoisomerase, Senna macranthera, Fabaceae.ABSTRACT: "Rubrofusarin, a natural polyketide as new human topoisomerase IIinhibitor". This work describes the inhibitory effect of rubrofusarin (5,6-dihydroxy-8-methoxy-2-methylbenzo[g]cromen-4-one, 1) against human DNA topoisomerase II-. The results for relaxation assays showed total inhibition of topisomerase II-by rubrofusarin at 120 M. This result is comparable to the one observed with etoposide as positive control. For this study, rubrofusarin was isolated from Senna macranthera var. nervosa (Voguel) Irwin & Barnebyem and characterized by spectral data, including 2D NMR, as well as its acetylated derivative.Keywords: Rubrofusarin, topoisomerase, Senna macranthera, Fabaceae. INTRODUÇÃOAs topoisomerases são enzimas nucleares que controlam e modifi cam o estado topológico do DNA. Estas enzimas nucleares são classifi cadas em tipo I e II, de acordo com seus mecanismos e propriedades físicas, em células de mamíferos. A topoisomerase II (Topo II), dímero de tamanho aproximado de 170 kDa e existente nas isoformas ou , é responsável pela quebra da fi ta dupla de DNA levando a eventos como liberação da fi ta de DNA enovelada, transcrição, condensação dos cromossomos e recombinação (Sampaio et al., 2006;Hande, 2006). As topoisomerases, durante a proliferação celular, participam da manutenção e replicação do DNA. Quando estas funções são desativadas, as células fi cam vulneráveis. Além disso, em tecidos tumorais a expressão das DNA-Topo I e II é maior do que nas células de metabolismo normal (Kellner et al., 2000). Assim, as topoisomerases são alvos importantes no desenvolvimento de novas drogas, principalmente para as que apresentam atividade anticâncer e antiviral (De Vita Jr et al., 1997).Na medicina destacam-se os compostos das classes das antraciclinas e das epipodofi lotoxinas como potentes inibidores da topoisomerase II. Estes compostos agem inibindo a religação do DNA e induzem a ligação de proteínas em suas quebras, e constituemse como parte integrante em quimioterapia de primeira linha para uma grande variedade de tumores sólidos e hematológicos (Sampaio et al., 2006). O etoposídeo, derivado semi-sintético da lignana podofi lotoxina, apresenta papel importante no tratamento clínico como potente agente quimioterapêutico para uma variedade de tumores, incluindo carcinomas, câncer testicular e linfomas (Zhang et al., 1992). Na tentativa de descobrir novos inibidores da...

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“…17 Several quinoline-based derivatives such as MK571, quinine, and primaquine are used in combination with other anticancer drugs to overcome multidrug resistance of some tumors. 18 Quinoline derivatives are also known as P-glycoprotein inhibitors, 19 topoisomerase I/II inhibitors, 20,21 PDGF receptor tyrosine kinase inhibitors, 22 and PI3-kinase-related kinases (PIKKs) inhibitors. 23 Some of these quinolines induce cell cycle arrest, 18,20 generation of reactive oxygen species (ROS), 24 disruption of mitochondrial membrane potential, 25 DNA single-strand breaks, 18 activation of caspases, 25 and interact with DNA.…”

Section: Introductionmentioning

confidence: 99%

“…18 Quinoline derivatives are also known as P-glycoprotein inhibitors, 19 topoisomerase I/II inhibitors, 20,21 PDGF receptor tyrosine kinase inhibitors, 22 and PI3-kinase-related kinases (PIKKs) inhibitors. 23 Some of these quinolines induce cell cycle arrest, 18,20 generation of reactive oxygen species (ROS), 24 disruption of mitochondrial membrane potential, 25 DNA single-strand breaks, 18 activation of caspases, 25 and interact with DNA. 20,21 Based on the above-mentioned effects of quinolines, a new series of substituted nitrogen atomcontaining heterocyclic compounds was prepared.…”

Section: Introductionmentioning

confidence: 99%

“…23 Some of these quinolines induce cell cycle arrest, 18,20 generation of reactive oxygen species (ROS), 24 disruption of mitochondrial membrane potential, 25 DNA single-strand breaks, 18 activation of caspases, 25 and interact with DNA. 20,21 Based on the above-mentioned effects of quinolines, a new series of substituted nitrogen atomcontaining heterocyclic compounds was prepared. These compounds were screened for antibacterial and cytotoxic activities in vitro.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

4‐Amino‐3‐acetylquinoline‐induced apoptosis of murine L1210 leukemia cells involves ROS‐mitochondrial‐mediated death signaling and activation of p38 MAPK

Jantová

Repicky

Letašiová

et al. 2008

Cell Biochemistry & Function

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Quinolines are known to be multitarget agents with a broad spectrum of biological activity. In a previous study, we showed that newly prepared 4-amino-3-acetylquinoline (AAQ) possesses strong anticancer activities. In this study, we investigated whether AAQ has cytotoxicity in murine L1210 leukemia cells. Results from cell proliferation assays showed that AAQ caused significant decrease in cell number in a dose-dependent manner. The cell death induced by AAQ appeared to involve apoptosis, based on evidence from apoptotic DNA fragmentation, flow cytometry, fluorescence microscopy, and Western blot analyses. We found that AAQ-treated cells had activated p38 MAPK and that apoptosis was processed through a reactive oxygen species (ROS)-dependent mitochondrial pathway. In summary, our results suggest that AAQ can induce apoptosis, at least in part, through the activation of the p38 MAPK pathway in L1210 leukemia cells.

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Lunacridine from Lunasia amara is a DNA intercalating topoisomerase II inhibitor

Cited by 42 publications

References 16 publications

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Rubrofusarina, um policetídeo natural inibidor da topoisomerase II-α humana

4‐Amino‐3‐acetylquinoline‐induced apoptosis of murine L1210 leukemia cells involves ROS‐mitochondrial‐mediated death signaling and activation of p38 MAPK

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