Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | http://ri.ufs.br/jspui/handle/riufs/12226 |
Resumo: | Cancer is a disease of high incidence, high mortality and difficult to treat, and there is therefore a constant social interest in the search for more effective therapies. In this sense, essential oils and their constituents are promising source of natural products as antitumor substances. Thus, the aim of this study was to evaluate the cytotoxic activity of 19 p-menthane derivatives structurally correlated with perillyl alcohol against three strains of human tumor cells: ovarian adenocarcinoma (OVCAR-8), colon carcinoma (HCT-116) and glioblastoma (SF-295) using the colorimetric MTT assay. The tests were performed in triplicate in a single concentration of 25 μg/ml. The results demonstrated that all substances tested were less cytotoxic than the perillyl alcohol, with the exception of 1,2-perillaldehyde epoxide (EP-1) and 8,9-periallaldehyde epoxide (EP-2) (IG = 95.66 to 99.89%) and IC50 ranging from 2.68 to 3.92 and 1.03 to 1.75 mg/ml, respectively. The perillyl benzoate was the least cytotoxic substance, with a value (GI = 2.86 to 5.02%). The monoterpenes (+)-limonene epoxide, (-)-hydroxy-carvone (-HC) and perillaldehyde had intermediate cytotoxic activity, with (IG = 58.40 to 94.01%). Given these results, the structural characteristics that can contribute to understand the cytotoxicity of perillyl alcohol and its analogs were identified. In general, substitution of C-C double bonds per epoxide groups added to the aldehyde group increased cytotoxicity. The presence and location of ketone and epoxide groups in p-menthane skeleton influence the cytotoxic activity. The addition of hydroxyl groups in the chemical structure resulted in less cytotoxic compounds, as was the case of the cis-carveol and sobrerol. As well, acetylation of such groups led to an overall decrease in cytotoxicity, indicating that lipophilicity plays a major role in the decrease of cytotoxic activity. In addition, the enantioselectivity to perform an important role in the cytotoxicity of natural compounds, as observed for (-)- and (+)-hydroxy-carvone. These results demonstrate that different functional groups and their positions in p-menthane skeleton influence the cytotoxic activity. Next was evaluated the in vivo antitumor activity of the compounds EP-1, EP-2 and (-HC) in Sarcoma 180-bearing mice (S180). In this test, the administration of EP-1 and EP-2 (100 or 200 mg/kg/day) inhibited the development in S180-inoculated mice. The inhibition was 33.4 and 56.4% for EP-1 and 38.4 and 58.7% for EP-2 at both doses, respectively. Already (-HC) (50 or 100 mg/kg/day) showed no antitumor activity in vivo. There were no changes in biochemical parameters in animals treated with EP-1 and EP-2. In relation to hematological analysis, these compounds showed a reduction in the number of total leukocytes and alterations in the differential count, a result expected as due to S180 tumor. The mechanism of action of EP-1 and EP-2 were then studied. None of the compounds tested induced hemolysis. The viability of HL-60 cells was affected by both monoterpenes after an exposure period of 24h, when analyzed by trypan blue exclusion. Both EP-1 and EP-2 reduced the number of viable cells associated with an increase in the number of non-viable cells, which contributes to the increased number of dead cells in the morphological analysis. The incorporation of ethidium bromide/acridine orange, the treated cells, cytotoxicity suggests apoptosis and necrosis pathway. Therefore, front of results, can conclude that EP-2 was more potent in vitro compared to EP-1, however, both substances showed cytotoxic activity through apoptotic and necrotic processes. These data suggest that EP-1 and EP-2 present a potential and promising anticancer potential and moreover, appropriate structural modifications are possible to develop novel anticancer agents. |
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Andrade, Luciana NaloneSousa, Damião Pergentino deCarvalho, Adriana Andrade2019-10-29T23:44:38Z2019-10-29T23:44:38Z2015-07-24ANDRADE, Luciana Nalone. Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais. 2015. 162 f. Tese (Doutorado em Biotecnologia) - Universidade Federal de Sergipe, São Cristóvão, SE, 2015.http://ri.ufs.br/jspui/handle/riufs/12226Cancer is a disease of high incidence, high mortality and difficult to treat, and there is therefore a constant social interest in the search for more effective therapies. In this sense, essential oils and their constituents are promising source of natural products as antitumor substances. Thus, the aim of this study was to evaluate the cytotoxic activity of 19 p-menthane derivatives structurally correlated with perillyl alcohol against three strains of human tumor cells: ovarian adenocarcinoma (OVCAR-8), colon carcinoma (HCT-116) and glioblastoma (SF-295) using the colorimetric MTT assay. The tests were performed in triplicate in a single concentration of 25 μg/ml. The results demonstrated that all substances tested were less cytotoxic than the perillyl alcohol, with the exception of 1,2-perillaldehyde epoxide (EP-1) and 8,9-periallaldehyde epoxide (EP-2) (IG = 95.66 to 99.89%) and IC50 ranging from 2.68 to 3.92 and 1.03 to 1.75 mg/ml, respectively. The perillyl benzoate was the least cytotoxic substance, with a value (GI = 2.86 to 5.02%). The monoterpenes (+)-limonene epoxide, (-)-hydroxy-carvone (-HC) and perillaldehyde had intermediate cytotoxic activity, with (IG = 58.40 to 94.01%). Given these results, the structural characteristics that can contribute to understand the cytotoxicity of perillyl alcohol and its analogs were identified. In general, substitution of C-C double bonds per epoxide groups added to the aldehyde group increased cytotoxicity. The presence and location of ketone and epoxide groups in p-menthane skeleton influence the cytotoxic activity. The addition of hydroxyl groups in the chemical structure resulted in less cytotoxic compounds, as was the case of the cis-carveol and sobrerol. As well, acetylation of such groups led to an overall decrease in cytotoxicity, indicating that lipophilicity plays a major role in the decrease of cytotoxic activity. In addition, the enantioselectivity to perform an important role in the cytotoxicity of natural compounds, as observed for (-)- and (+)-hydroxy-carvone. These results demonstrate that different functional groups and their positions in p-menthane skeleton influence the cytotoxic activity. Next was evaluated the in vivo antitumor activity of the compounds EP-1, EP-2 and (-HC) in Sarcoma 180-bearing mice (S180). In this test, the administration of EP-1 and EP-2 (100 or 200 mg/kg/day) inhibited the development in S180-inoculated mice. The inhibition was 33.4 and 56.4% for EP-1 and 38.4 and 58.7% for EP-2 at both doses, respectively. Already (-HC) (50 or 100 mg/kg/day) showed no antitumor activity in vivo. There were no changes in biochemical parameters in animals treated with EP-1 and EP-2. In relation to hematological analysis, these compounds showed a reduction in the number of total leukocytes and alterations in the differential count, a result expected as due to S180 tumor. The mechanism of action of EP-1 and EP-2 were then studied. None of the compounds tested induced hemolysis. The viability of HL-60 cells was affected by both monoterpenes after an exposure period of 24h, when analyzed by trypan blue exclusion. Both EP-1 and EP-2 reduced the number of viable cells associated with an increase in the number of non-viable cells, which contributes to the increased number of dead cells in the morphological analysis. The incorporation of ethidium bromide/acridine orange, the treated cells, cytotoxicity suggests apoptosis and necrosis pathway. Therefore, front of results, can conclude that EP-2 was more potent in vitro compared to EP-1, however, both substances showed cytotoxic activity through apoptotic and necrotic processes. These data suggest that EP-1 and EP-2 present a potential and promising anticancer potential and moreover, appropriate structural modifications are possible to develop novel anticancer agents.O câncer é uma doença de grande incidência, alta mortalidade e de difícil tratamento, havendo, portanto, um constante interesse social na procura por terapias mais eficientes. Nesse sentido, os óleos essenciais e seus constituintes químicos têm se mostrado como potenciais agentes bioativos antitumorais. Sendo assim, o objetivo do presente estudo foi avaliar a atividade citotóxica de 19 derivados p-mentânicos estruturalmente relacionadas ao álcool perílico frente a 3 linhagens de células tumorais humanas: adenocarcinoma ovariano (OVCAR-8), carcinoma de cólon (HCT-116) e glioblastoma (SF-295) através do ensaio colorimétrico de MTT. Essas substâncias foram avaliadas de acordo com o grau de inibição da proliferação celular (GI%), visando identificar as substâncias mais citotóxicas e as características moleculares que contribuem para a atividade in vitro. Os testes foram realizados em triplicata com concentração única de 25 μg/mL. Os resultados demostraram que todas as substâncias testadas foram menos citotóxicas do que o álcool perílico, com exceção do 1,2-epóxi-perialdeído (EP-1) e 8,9-epóxi-perialdeído (EP-2) (GI = 95,66 a 99,89%), com CI50 variando entre 2,68 a 3,92 e 1,03 a 1,75 μg/mL, respectivamente. O benzoato de perila foi a substância menos citotóxica, com um valor de (GI = 2,86 a 5,02%). As substâncias (+)-1,2-epóxi-limoneno, (-)-hidróxi-carvona (-HC) e perialdeído apresentaram atividade citotóxica intermediária, com (GI = 58,40 a 94,01%). Diante desses resultados, as características estruturais que podem contribuir para compreender a atividade citotóxica do álcool perílico e seus análogos foram identificadas. Em geral, a substituição de duplas ligações C-C por grupos epóxido somado ao grupo aldeído aumentou a citotoxicidade. A presença e a posição dos grupos cetona e epóxido no esqueleto p-mentano influenciaram na atividade citotóxica. A adição de grupos hidroxila na estrutura química resultou em substâncias menos citotóxicas, como foi o caso do cis-carveol e sobrerol. Como também, a acetilação de tais grupos conduziu a uma diminuição global da citotoxicidade, indicando que a lipofilicidade desempenha um papel importante na diminuição da atividade citotóxica. Além disso, a enantiosseletividade pode desempenhar um papel importante na citotoxicidade de substâncias naturais, como observado para a (-)- e (+)-hidróxi-carvona. Esses resultados demonstram que os diferentes grupos funcionais e as suas posições no esqueleto p-mentano influenciam na atividade citotóxica. Em seguida, foi avaliada a atividade antitumoral in vivo das substâncias com maior citotoxicidade e sem estudos prévios descritos na literatura, EP-1, EP-2 e (-HC) utilizando camundongos transplantados com Sarcoma 180 (S180). Neste ensaio, a administração de EP-1 ou EP-2 (100 ou 200 mg/kg/dia) inibiu o desenvolvimento de tumor sólido em camundongos transplantados com S180. A inibição foi de 33,4 e 56,4% para EP-1 e 38,4 e 58,7% para EP-2 em ambas as doses, respectivamente. Já a (-HC) não apresentou atividade antitumoral in vivo em nenhuma das doses testadas. Não houve alterações nos parâmetros bioquímicos em animais tratados com EP-1 e EP-2. Em relação às análises hematológicas, essas substâncias demonstraram redução no número de leucócitos totais e alterações na contagem diferencial. O mecanismo de ação de EP-1 e EP-2 foram, então, estudados. Nenhuma das substâncias testadas induziu hemólise. A viabilidade de células HL-60 foi afetada por ambas as substâncias após um período de exposição de 24h, quando analisada por exclusão por azul de tripan. Tanto EP-1 quanto EP-2 reduziram o número de células viáveis associado com um aumento no número de células não viáveis, o que colabora com o aumento do número de células mortas na análise morfológica. A incorporação do brometo de etídio/laranja de acridina, nas células tratadas, sugere citotoxicidade via apoptose e necrose. Logo, diante dos resultados, podemos concluir que EP-2 foi mais potente in vitro comparado a EP-1, entretanto, ambas as substâncias apresentaram atividade citotóxica através dos processos apoptótico e necrótico. Esses dados sugerem que EP-1 e EP-2 apresentam um potencial anticâncer promissor e além disso, modificações estruturais adequadas são possíveis para o desenvolvimento de novos agentes antitumoraisSão Cristóvão, SEporBiotecnologiaCâncerCitotoxicidadeAgentes antineoplásicosP-mentânicosCitotoxicidadeAtividade antitumoralP-menthane monoterpenesCytotoxicityAntitumor activityOUTROSDerivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumoraisP-Menthane derivatives: relationship studies structure-activity and new assessment candidates antitumor agentsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Biotecnologia (RENORBIO-SE)UFSreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/12226/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALLUCIANA_NALONE_ANDRADE.pdfLUCIANA_NALONE_ANDRADE.pdfapplication/pdf3724061https://ri.ufs.br/jspui/bitstream/riufs/12226/2/LUCIANA_NALONE_ANDRADE.pdfe1c60b6d73961cc046153847e1e5e8d6MD52TEXTLUCIANA_NALONE_ANDRADE.pdf.txtLUCIANA_NALONE_ANDRADE.pdf.txtExtracted texttext/plain304036https://ri.ufs.br/jspui/bitstream/riufs/12226/3/LUCIANA_NALONE_ANDRADE.pdf.txt79c9dd75c3c07088bcda8cde7cd31a2bMD53THUMBNAILLUCIANA_NALONE_ANDRADE.pdf.jpgLUCIANA_NALONE_ANDRADE.pdf.jpgGenerated Thumbnailimage/jpeg1330https://ri.ufs.br/jspui/bitstream/riufs/12226/4/LUCIANA_NALONE_ANDRADE.pdf.jpg11c52843fa5e5f3a0be12db55044a19eMD54riufs/122262024-01-17 16:56:04.33oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2024-01-17T19:56:04Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
dc.title.alternative.eng.fl_str_mv |
P-Menthane derivatives: relationship studies structure-activity and new assessment candidates antitumor agents |
title |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
spellingShingle |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais Andrade, Luciana Nalone Biotecnologia Câncer Citotoxicidade Agentes antineoplásicos P-mentânicos Citotoxicidade Atividade antitumoral P-menthane monoterpenes Cytotoxicity Antitumor activity OUTROS |
title_short |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
title_full |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
title_fullStr |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
title_full_unstemmed |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
title_sort |
Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais |
author |
Andrade, Luciana Nalone |
author_facet |
Andrade, Luciana Nalone |
author_role |
author |
dc.contributor.author.fl_str_mv |
Andrade, Luciana Nalone |
dc.contributor.advisor1.fl_str_mv |
Sousa, Damião Pergentino de |
dc.contributor.advisor-co1.fl_str_mv |
Carvalho, Adriana Andrade |
contributor_str_mv |
Sousa, Damião Pergentino de Carvalho, Adriana Andrade |
dc.subject.por.fl_str_mv |
Biotecnologia Câncer Citotoxicidade Agentes antineoplásicos P-mentânicos Citotoxicidade Atividade antitumoral |
topic |
Biotecnologia Câncer Citotoxicidade Agentes antineoplásicos P-mentânicos Citotoxicidade Atividade antitumoral P-menthane monoterpenes Cytotoxicity Antitumor activity OUTROS |
dc.subject.eng.fl_str_mv |
P-menthane monoterpenes Cytotoxicity Antitumor activity |
dc.subject.cnpq.fl_str_mv |
OUTROS |
description |
Cancer is a disease of high incidence, high mortality and difficult to treat, and there is therefore a constant social interest in the search for more effective therapies. In this sense, essential oils and their constituents are promising source of natural products as antitumor substances. Thus, the aim of this study was to evaluate the cytotoxic activity of 19 p-menthane derivatives structurally correlated with perillyl alcohol against three strains of human tumor cells: ovarian adenocarcinoma (OVCAR-8), colon carcinoma (HCT-116) and glioblastoma (SF-295) using the colorimetric MTT assay. The tests were performed in triplicate in a single concentration of 25 μg/ml. The results demonstrated that all substances tested were less cytotoxic than the perillyl alcohol, with the exception of 1,2-perillaldehyde epoxide (EP-1) and 8,9-periallaldehyde epoxide (EP-2) (IG = 95.66 to 99.89%) and IC50 ranging from 2.68 to 3.92 and 1.03 to 1.75 mg/ml, respectively. The perillyl benzoate was the least cytotoxic substance, with a value (GI = 2.86 to 5.02%). The monoterpenes (+)-limonene epoxide, (-)-hydroxy-carvone (-HC) and perillaldehyde had intermediate cytotoxic activity, with (IG = 58.40 to 94.01%). Given these results, the structural characteristics that can contribute to understand the cytotoxicity of perillyl alcohol and its analogs were identified. In general, substitution of C-C double bonds per epoxide groups added to the aldehyde group increased cytotoxicity. The presence and location of ketone and epoxide groups in p-menthane skeleton influence the cytotoxic activity. The addition of hydroxyl groups in the chemical structure resulted in less cytotoxic compounds, as was the case of the cis-carveol and sobrerol. As well, acetylation of such groups led to an overall decrease in cytotoxicity, indicating that lipophilicity plays a major role in the decrease of cytotoxic activity. In addition, the enantioselectivity to perform an important role in the cytotoxicity of natural compounds, as observed for (-)- and (+)-hydroxy-carvone. These results demonstrate that different functional groups and their positions in p-menthane skeleton influence the cytotoxic activity. Next was evaluated the in vivo antitumor activity of the compounds EP-1, EP-2 and (-HC) in Sarcoma 180-bearing mice (S180). In this test, the administration of EP-1 and EP-2 (100 or 200 mg/kg/day) inhibited the development in S180-inoculated mice. The inhibition was 33.4 and 56.4% for EP-1 and 38.4 and 58.7% for EP-2 at both doses, respectively. Already (-HC) (50 or 100 mg/kg/day) showed no antitumor activity in vivo. There were no changes in biochemical parameters in animals treated with EP-1 and EP-2. In relation to hematological analysis, these compounds showed a reduction in the number of total leukocytes and alterations in the differential count, a result expected as due to S180 tumor. The mechanism of action of EP-1 and EP-2 were then studied. None of the compounds tested induced hemolysis. The viability of HL-60 cells was affected by both monoterpenes after an exposure period of 24h, when analyzed by trypan blue exclusion. Both EP-1 and EP-2 reduced the number of viable cells associated with an increase in the number of non-viable cells, which contributes to the increased number of dead cells in the morphological analysis. The incorporation of ethidium bromide/acridine orange, the treated cells, cytotoxicity suggests apoptosis and necrosis pathway. Therefore, front of results, can conclude that EP-2 was more potent in vitro compared to EP-1, however, both substances showed cytotoxic activity through apoptotic and necrotic processes. These data suggest that EP-1 and EP-2 present a potential and promising anticancer potential and moreover, appropriate structural modifications are possible to develop novel anticancer agents. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-07-24 |
dc.date.accessioned.fl_str_mv |
2019-10-29T23:44:38Z |
dc.date.available.fl_str_mv |
2019-10-29T23:44:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ANDRADE, Luciana Nalone. Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais. 2015. 162 f. Tese (Doutorado em Biotecnologia) - Universidade Federal de Sergipe, São Cristóvão, SE, 2015. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/12226 |
identifier_str_mv |
ANDRADE, Luciana Nalone. Derivados p-Mentânicos : estudos de relação estrutura-atividade e avaliação de novos candidatos a agentes antitumorais. 2015. 162 f. Tese (Doutorado em Biotecnologia) - Universidade Federal de Sergipe, São Cristóvão, SE, 2015. |
url |
http://ri.ufs.br/jspui/handle/riufs/12226 |
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por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.program.fl_str_mv |
Pós-Graduação em Biotecnologia (RENORBIO-SE) |
dc.publisher.initials.fl_str_mv |
UFS |
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Universidade Federal de Sergipe (UFS) |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS) |
repository.mail.fl_str_mv |
repositorio@academico.ufs.br |
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1802110744510070784 |