Quantitative structure activity relationships studies for antimicrobial activity of para and meta substituted N,N-[(dimethylaminoethyl) benzoates chlorides evaluated against Saccharomyces cerevisiae (BY4741) and Escherichia coli (DH5α).

No presente trabalho, destinado a tese de doutorado, desenvolvemos um estudo da relação entre a estrutura química e atividade antimicrobiana de duas séries, a saber: Série I - quatorze cloretos N,N[(dimetilamino)etil]-benzoatos para-substituídos, onde R4 = H, CH3, C2H5, nC4H9, tC4H9, OCH3, nOC4H9, COCH3, Cl, CN, NO2, OC6H13, SO2Me, CF3 (compostos I.1 a I.14) e Série II - quatorze cloretos meta-substituídos onde R3 = H, -CH3, -OCH3, -OC2H5, -OC4H9, -F, -Cl, -Br, -I, -NO2, -CN, -CF3, -N(CH3)2, SO2CH3 (compostos II.1. a II.14). Os compostos haviam sido sintetizados anteriormente no grupo (Amaral et al, 1997; Sousa, 1997). Para as séries I e II, os valores do coeficiente de partição em n-octanol foram obtidos por cálculo (utilizando os programas CLOGP e ACD/LogP) bem como determinados experimentalmente pelo método CLAE e considerados parâmetros lipofílicos nos modelos de QSAR. Adicionalmente, para as séries I e II, os valores da posição da banda de absorção da carbonila na região do infravermelho bem como do deslocamento químico da carbonila no RMN 13C foram determinados sendo o primeiro considerado como parâmetro eletrônico nos modelos QSAR. E, ainda, para as séries I e II os valores de MR3 e de MR4 , relacionados à refratividade molar, foram obtidos da literatura e considerados nas análises QSAR . Para as séries I e II os valores de IC50 (concentração inibição 50% do crescimento) foram determinados contra, respectivamente, o fungo Saccharomyces cerevisiae (BY4741) e contra a bactéria Escherichia coli (DH5α) e considerados como parâmetros biológico nas análises QSAR. Para as séries I e II e para as séries I e II reunidas, foram gerados modelos QSAR e estes foram analisados visando avaliar a natureza e a contribuição de cada parâmetro estrutural para cada uma das atividades avaliadas. A aplicação do modelo linear resultou em modelos iestatisticamente significativos para as atividades contra o Saccharomyces cerevisiae (BY4741) e contra a Escherichia coli (DH5α) para a série I e para as séries I e II reunidas. A série II não gerou modelos lineares estatisticamente significativos. A aplicação dos modelos bilinear e parabólico foram verificadas não resultando em modelos estatisticamente significativos. Para a série I e para as séries I e II reunidas estudadas neste trabalho, as diferenças observadas nos modelos QSAR gerados para a inibição do crescimento de, respectivamente, S. cerevisiae (BY4741) e de E. coli (DH5α) podem ser, possivelmente, explicadas considerando-se as diferenças nas membranas externas de cada microorganismo.In this PhD thesis work, we developed a quantitative structure relationship study for the antimicrobial activity of two series, namely: Series I fourteen para-substituted N,N- [(dimethylamino)ethyl)] benzoates chlorides, where R4 = -H, -CH3, -C2H5, -nC4H9, -tC4H9, -OCH3, - nOC4H9, -COCH3, -Cl, -CN, -NO2, -OC6H13, -SO2Me, -CF3 (compounds I.1 - I.14) and Series II - fourteen meta-substituted chlorides, where R3 = -H, -CH3, -OCH3, -OC2H5, -OC4H9, -F, -Cl, -Br, -I, -NO2, -CN, -CF3, -N(CH3)2, -SO2CH3 (compounds II.1. - II.14). These compounds had been previously synthesized in the group (Amaral et al, 1997; Sousa, 1997). For series I and II, the partition coefficient values in n-octanol were obtained by calculation (using the CLOGP and the ACD/LogP programs) and were obtained experimentally by HPLC method. These values were taken as lipophilic parameters in the QSAR analysis. In addition, for the series I and II, the carbonyl infrared absorption band values and 13C-NMR chemical shifts of carbonyl group were determined, being the former considered as electronic parameters in the QSAR analysis. Further, for the series I and II, the MR3 and MR4 values were taken from the literature and considered as molar refractivity related parameter in the QSAR analyses. For the series I and II, IC50 values (concentration inhibiting 50% growth) were determined against, respectively, Saccharomyces cerevisiae (BY4741) yeast and Escherichia coli (DH5α) bacteria and taken as biological parameters in the QSAR analysis. For the series I and II and for series I e II altogether, QSAR models were generated and analysed in order to determine the nature and the contribution of each structural parameter to the determined antimicrobial activities. The application of linear model resulted in statistically significant QSAR models for the activities evaluated against Saccharomyces cerevisiae (BY4741) and against Escherichia coli (DH5α) for series I and for series I and II taken altogether. No statistically significant linear models were obtained for series II. The application of bilinear and parabolic models was verified, resulting in no statistically significant models. For series I and series I e II altogether, the differences observed in the generated QSAR models for the inhibition, respectively, of Saccharomyces cerevisiae (BY4741) and of E. coli (DH5α) growth, can be, probably, explained considering the differences in the external membranes of each microorganism

Quantitative structure activity relationships studies for antimicrobial activity of para and meta substituted N,N-[(dimethylaminoethyl) benzoates chlorides evaluated against Saccharomyces cerevisiae (BY4741) and Escherichia coli (DH5α).

No presente trabalho, destinado a tese de doutorado, desenvolvemos um estudo da relação entre a estrutura química e atividade antimicrobiana de duas séries, a saber: Série I - quatorze cloretos N,N[(dimetilamino)etil]-benzoatos para-substituídos, onde R4 = H, CH3, C2H5, nC4H9, tC4H9, OCH3, nOC4H9, COCH3, Cl, CN, NO2, OC6H13, SO2Me, CF3 (compostos I.1 a I.14) e Série II - quatorze cloretos meta-substituídos onde R3 = H, -CH3, -OCH3, -OC2H5, -OC4H9, -F, -Cl, -Br, -I, -NO2, -CN, -CF3, -N(CH3)2, SO2CH3 (compostos II.1. a II.14). Os compostos haviam sido sintetizados anteriormente no grupo (Amaral et al, 1997; Sousa, 1997). Para as séries I e II, os valores do coeficiente de partição em n-octanol foram obtidos por cálculo (utilizando os programas CLOGP e ACD/LogP) bem como determinados experimentalmente pelo método CLAE e considerados parâmetros lipofílicos nos modelos de QSAR. Adicionalmente, para as séries I e II, os valores da posição da banda de absorção da carbonila na região do infravermelho bem como do deslocamento químico da carbonila no RMN 13C foram determinados sendo o primeiro considerado como parâmetro eletrônico nos modelos QSAR. E, ainda, para as séries I e II os valores de MR3 e de MR4 , relacionados à refratividade molar, foram obtidos da literatura e considerados nas análises QSAR . Para as séries I e II os valores de IC50 (concentração inibição 50% do crescimento) foram determinados contra, respectivamente, o fungo Saccharomyces cerevisiae (BY4741) e contra a bactéria Escherichia coli (DH5α) e considerados como parâmetros biológico nas análises QSAR. Para as séries I e II e para as séries I e II reunidas, foram gerados modelos QSAR e estes foram analisados visando avaliar a natureza e a contribuição de cada parâmetro estrutural para cada uma das atividades avaliadas. A aplicação do modelo linear resultou em modelos iestatisticamente significativos para as atividades contra o Saccharomyces cerevisiae (BY4741) e contra a Escherichia coli (DH5α) para a série I e para as séries I e II reunidas. A série II não gerou modelos lineares estatisticamente significativos. A aplicação dos modelos bilinear e parabólico foram verificadas não resultando em modelos estatisticamente significativos. Para a série I e para as séries I e II reunidas estudadas neste trabalho, as diferenças observadas nos modelos QSAR gerados para a inibição do crescimento de, respectivamente, S. cerevisiae (BY4741) e de E. coli (DH5α) podem ser, possivelmente, explicadas considerando-se as diferenças nas membranas externas de cada microorganismo.In this PhD thesis work, we developed a quantitative structure relationship study for the antimicrobial activity of two series, namely: Series I fourteen para-substituted N,N- [(dimethylamino)ethyl)] benzoates chlorides, where R4 = -H, -CH3, -C2H5, -nC4H9, -tC4H9, -OCH3, - nOC4H9, -COCH3, -Cl, -CN, -NO2, -OC6H13, -SO2Me, -CF3 (compounds I.1 - I.14) and Series II - fourteen meta-substituted chlorides, where R3 = -H, -CH3, -OCH3, -OC2H5, -OC4H9, -F, -Cl, -Br, -I, -NO2, -CN, -CF3, -N(CH3)2, -SO2CH3 (compounds II.1. - II.14). These compounds had been previously synthesized in the group (Amaral et al, 1997; Sousa, 1997). For series I and II, the partition coefficient values in n-octanol were obtained by calculation (using the CLOGP and the ACD/LogP programs) and were obtained experimentally by HPLC method. These values were taken as lipophilic parameters in the QSAR analysis. In addition, for the series I and II, the carbonyl infrared absorption band values and 13C-NMR chemical shifts of carbonyl group were determined, being the former considered as electronic parameters in the QSAR analysis. Further, for the series I and II, the MR3 and MR4 values were taken from the literature and considered as molar refractivity related parameter in the QSAR analyses. For the series I and II, IC50 values (concentration inhibiting 50% growth) were determined against, respectively, Saccharomyces cerevisiae (BY4741) yeast and Escherichia coli (DH5α) bacteria and taken as biological parameters in the QSAR analysis. For the series I and II and for series I e II altogether, QSAR models were generated and analysed in order to determine the nature and the contribution of each structural parameter to the determined antimicrobial activities. The application of linear model resulted in statistically significant QSAR models for the activities evaluated against Saccharomyces cerevisiae (BY4741) and against Escherichia coli (DH5α) for series I and for series I and II taken altogether. No statistically significant linear models were obtained for series II. The application of bilinear and parabolic models was verified, resulting in no statistically significant models. For series I and series I e II altogether, the differences observed in the generated QSAR models for the inhibition, respectively, of Saccharomyces cerevisiae (BY4741) and of E. coli (DH5α) growth, can be, probably, explained considering the differences in the external membranes of each microorganism

Cytotoxic fractions from the leaves of Tachia grandiflora

This work is part of a larger screening program, which seeks to discover new antitumor plants and compounds from the Brazilian Amazon. In a prescreen of stem and leaf extracts of Tachia grandiflora Maguire & Weaver (Gentianaceae) based on the SRB method, leaf methanol and ethanol extracts showed appreciable cytotoxicity in human breast (MCF-7) and colon (HCT-8) tumor cell lines. Liquid-liquid partitioning of the leaf ethanol extract yielded hexane, chloroform, butanol, and water-methanol fractions. Only the hexane and chloroform fractions were active, inhibiting murine melanoma (B-16) and HCT-8 cells. The chloroform fraction suffered sequential column chromatography on silica gel using different eluent systems and yielded a number of very active subfractions. In all, 25 fractions and subfractions were tested, and 10 exhibited high growth inhibition of HCT-8, and two of these presented strong inhibition of murine melanoma (B-16) cells. The most active subfractions were tested against five tumor cell lines (leukemia CEM and HL-60, as well as the three used previously) using the MTT assay, and four fractions demonstrated significant cytotoxicity based on IC50. Cell lysis was discarded as a possible mechanism for in vitro cytotoxicity given that these fractions did not exhibit hemolytic activity. The greatest antiproliferative potential was found in the second (two samples) and third generation (two samples) chromatographic subfractions of the chloroform fraction (obtained from partitioning of the ethanol extract). These subfractions proved to be complex mixtures from which no pure substance could be isolated after further chromatographic separations. © 2007 Informa Healthcare

Screening of plants found in Amazonas State for lethality towards brine shrimp

226 methanol and water extracts representing 74 mainly native plant species found in Amazonas State, Brazil, were tested at a standard concentration of 500 μg/mL for lethality towards larvae of the brine shrimp species Artemia franciscana. Several cytotoxic plant species were identified in this work: Aspidosperma marcgravianum, A. nitidum, Croton cajucara, Citrus limetta, Geissospermum argenteum, Minquartia guianensis, Piper aduncum, P. amapense, P. capitarianum, P. tuberculatum and Protium aracouchini. The results were analyzed within the context of the available traditional knowledge and uses for these plants

Screening of plants found in the State of Amazonas, Brazil for activity against Aedes aegypti larvae Triagem de plantas encontradas no Estado do Amazonas para atividade larvicida contra Aedes aegypti

Ethanol, methanol and water extracts representing mostly native plant species found in the Amazon region were prepared, respectively, by maceration, continuous liquid-solid extraction and infusion, followed by evaporation and freeze-drying. The freeze-dried extracts were tested for lethality toward Aedes aegypti larvae at test concentrations of 500 mg / mL. In general, methanol extracts exhibited the greatest larvicidal activity. The following 7 methanol extracts of (the parts of) the indicated plant species were the most active, resulting in 100% mortality in A. aegypti larvae: Tapura amazonica Poepp. (root), Piper aduncum L. (leaf and root), P. tuberculatum Jacq. (leaf, fruit and branch). and Simaba polyphylla (Cavalcante) W.W. Thomas (branch).<br>Extratos aquosos, etanólicos e metanólicos, representando principalmente espécies vegetais nativas encontradas na região Amazônica, foram preparados, respectivamente, por infusão, maceração e extração contínua líquido-sólido, seguida de evaporação e liofilização. Os extratos liofilizados foram testados para atividade contra larvas de Aedes aegypti, na concentração única de 500 mg / mL. Os extratos metanólicos foram, em geral, os que apresentaram maior atividade larvicida. Os seguintes 7 extratos metanólicos das (partes das) espécies vegetais indicadas foram os mais ativos, provocando 100% de mortalidade em larvas de A. aegypti: Tapura amazonica Poepp. (raiz), Piper aduncum L. (folha e raiz), P. tuberculatum Jacq. (folha, fruto e galho) e Simaba polyphylla (Cavalcante) W.W. Thomas (galho)