Synthesis, in vitro antiproliferative and anti-mycobacterium tuberculosis activities of novel β-carboline derivatives

A series of β-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline (24.9 μg mL-1) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline (26.9 μg mL-1) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI50) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (27.8 μg mL-1) and 1-(3-nitrophenyl)-3-carboxamide(ethyl) guanidine β-carboline (37.4 μg mL-1) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (GI50 = 0.45 mmol L-1) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability.27813981405CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESSem informaçãoSem informaçã

Synthesis, In Vitro Antiproliferative And Anti-mycobacterium Tuberculosis Activities Of Novel β-carboline Derivatives

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)A series of β-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline (24.9 μg mL-1) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline (26.9 μg mL-1) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI50) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (27.8 μg mL-1) and 1-(3-nitrophenyl)-3-carboxamide(ethyl) guanidine β-carboline (37.4 μg mL-1) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (GI50 = 0.45 mmol L-1) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability. © 2016 Sociedade Brasileira de Química.27813981405CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Produção De Biomassa E Conteúdo De Fenóis E Flavonoides De Schinus Terebinthifolius Cultivada Em Fileira Simples E Dupla Com Cama De Frango

The aim of this study was to evaluate the influence of the addition of poultry litter on growth, biomass yield, flavonoid and phenol content, and antioxidant activity in leaves of pink pepper. The experiment was carried out at the Federal University of Grande Dourados, in Dourados, Mato Grosso do Sul state, from October 2009 to May 2010. Pink pepper was grown in single or double row in soil with incorporated poultry litter at doses of 0, 5, 10, 15 and 20 t ha-1. Treatments were arranged as 2 x 5 factorial in a randomized block design with four replications. There was a significant interaction between the doses of poultry litter and evaluation times for plant height and chlorophyll content. A linear increase in leaf area, fresh and dry weight of leaves and diameter of main stems with increasing doses of poultry litter was observed. Plants grown in single row showed higher fresh weight of stem with increasing doses of poultry litter. Poultry litter at 15 and 20 t ha-1 promoted an increase in flavonoid and phenolic contents in the leaves. No significant effect on the antioxidant activity was observed by the chemical method using DPPH. Therefore, it is recommended the cultivation of pink pepper plants with double row and 20 t ha-1 of poultry litter to higher growth, biomass yield, and flavonoid and phenol content. © 2016, Universidade Federal de Santa Maria. All rights reserved.26378779

Influence of poultry litter and plant density on the production and chemical composition of the essential oil of Schinus terebinthifolius Raddi fruits

The aim of this study was to evaluate the production and chemical composition of the essential oil of Brazilian pepper fruits grown in single and double rows using different doses of semi decomposed poultry litter in two evaluation times. The experiment was carried out at the Federal University of Grande Dourados, in the city of Dourados, state o- Mato Grosso do Sul, Brazil, from October 2009 to November 2010. Brazilian pepper plants were grown in single and double rows in soil with incorporated poultry litter at the doses of 0, 5, 10, 15 and 20 t ha-1. Treatments were arranged as a 2 x 5 factorial experiment in a randomized block design with four replications. Fruits were harvested 180 and 390 days after transplant (DAT). There was a significant interaction for fresh weight of fruits and weight of 50 fruits, being the values higher at 180 DAT in the double rows with increasing poultry litter doses. Fruits harvested 390 DAT showed higher diameter compared with those harvested 180 DAT. The number of fruits per bunch was significantly influenced by the doses of poultry litter, presenting a linear increase with increasing doses. The essential oil of the Brazilian pepper fruits obtained by hydrodistillation and analyzed by Gas chromatography - mass spectrometry exhibited predominance of monoterpenes, highlighting α-pinene (20.14%) as the major constituent. The chemical composition of the essential oil was not influenced by the number of plant rows in the plot or by the doses of poultry litter in any evaluation time. Therefore, the cultivation of Brazilian pepper plants is recommended in double rows, with 13.59 t ha-1 of incorporated poultry litter in the soi, and with harvest of 180 DAT for higher fruit production

Total biomass and essential oil composition of Ocimum gratissimum L. in response to broiler litter and phosphorus

The aim of this experiment was to evaluate the biomass yield and chemical composition of the essential oil of clove basil in response to doses of broiler litter (0, 5, 10, 15 and 20 t ha-1) added in presence of triple superphosphate (200 kg ha-1) or without it. Before the first harvest, the height of the plants increased significantly (34.42 cm) when 15 tonnes ha-1 broiler litter were added to the soil. However, after resprouting, the plant heights ranged only as a function of the vegetative cycle, with maximum height (76.0 cm) observed at 60 days. Phosphate fertilization also significantly influenced the leaf area (1.771 cm2 plant-1) during the first harvest. The fresh weight of leaves increased linearly in response to the addition of broiler litter (20 ton ha-1) with maximum yields of 1,709 and 7,140 kg ha-1 during the first harvest and regrowth, respectively. On average, the oil content of the leaves was 0.7%, with maximum performance (3.8 L ha-1) when 20 tonnes ha-1 of broiler litter were added on the soil. Eugenol was found to be the major compound of the essential oil (71.65%)

Chemical Composition And Free Radical-scavenging, Anticancer And Anti-inflammatory Activities Of The Essential Oil From Ocimum Kilimandscharicum

Objective The essential oil from the leaves of Ocimum kilimandscharicum (EOOK), collected in Dourados-MS, was investigated for anticancer, anti-inflammatory and antioxidant activity and chemical composition. Materials and methods The essential oil was extracted by hydrodistillation, and the chemical composition was performed by gas chromatography-mass spectrometry. The essential oil was evaluated for free radical-scavenging activity using the DPPH assay and was tested in an anticancer assay against ten human cancer cell lines. The response parameter (GI50) was calculated for the cell lines tested. The anti-inflammatory activity was evaluated using carrageenan-induced pleurisy in mice. Results The chemical composition showed 45 components with a predominance of monoterpenes, such as camphor (51.81%), 1,8 cineole (20.13%) and limonene (11.23%). The EOOK exhibited potent free radical-scavenging activity by the DPPH assay with a GI50 of 8.31 μg/ml. The major constituents, pure camphor (IC50 = 12.56 μg/ml) and mixture of the limonene: 1, 8 cineole (IC50 = 23.25 μg/ml) displayed a potent activity. The oral administration of EOOK (at 30 and 100 mg kg-1), as well as the pure camphor or a mixture of 1,8 cineole with limonene, significantly inhibited the carrageenan (Cg) induced pleurisy, reducing the migration of total leukocytes in mice by 82 ± 4% (30 mg kg-1 of EOOK), 95 ± 4% (100 mg kg-1 of EOOK), 83 ± 9% (camphor) and 80 ± 5% (mixture of 1,8 cineole:limonene 1:1). In vitro cytotoxicity screening against a human ovarian cancer cell line displayed high selectivity and potent anticancer activity with GI50 = 31.90 mg ml-1. This work describes the anti-inflammatory, anticancer and antioxidant effects of EOOK for the first time. Conclusions The essential oil exhibited marked anti-inflammatory, antioxidant and anticancer effects, an effect that can be attributed the presence of majorital compounds, and the response profiles from chemical composition differed from other oils collected in different locales. © 2014 Published by Elsevier GmbH.211112981302Adams, R.P., (2001) Identification of Essential Oil Components by Gas Chromatography/ Quadrupole Mass Spectroscopy, , Allured 456 pBanerjee, S., Welsch, C.W., Rao, A.R., Modulatory influence of camphor on the activities of hepatic carcinogen metabolizing enzymes and the levels of hepatic and extrahepatic reduced glutathione in mice (1995) Cancer Lett., 88, pp. 163-169Bekele, A.J., Obeng-Ofori, D., Hassanali, A., Evaluation of Ocimum kenyense (Ayobangira) as source of repellents, toxicants and protectants in storage against three major stored product insect pests (1997) Journal of Applied Entomology, 121 (3), pp. 169-173Bhattacharyya, P., Bishayee, A., Ocimum sanctum Linn. 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The absorption, distribution and excretion of d-limonene in rats (1974) Xenobiotica, 4, pp. 77-84Jembere, B., Hassanali, A., Products derived from the leaves of Ocimum kilimandscharicum (Labiatae) as post harvest protectant against the infestation of three major stored product insect pests (2001) Bull. Entomol. Res., 85, pp. 361-367Joshi, R.K., Chemical composition, in vitro antimicrobial and antioxidant activities of the essential oils of Ocimum gratissimum, O. Sanctum and their major constituents (2013) Indian J. Pharmaceut. 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Synthesis And Antitumoral Activity Of Novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) And 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline Derivatives

Several novel 1-substituted-phenyl β-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI 50 < 100 μM) for all eight different types of human cancer cell lines tested. The β-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI 50 values lying in the nanomolar concentration range (GI 50 = 10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) β-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI 50 = 0.06 μM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents. © 2008 Elsevier Ltd. All rights reserved.162296609667Tonin, L.T.D., Barbosa, V.A., Bocca, C.C., Ramos, E.R.F., Nakamura, C.V., Costa, W.F., daBasso, E.A., Sarragiotto, M.H., (2008) Eur. J. Med. Chem, , 10.1016/j.ejmech.2008.03.044Wang, Y.-H., Tang, J.-G., Wang, R.-R., Yang, L.-M., Dong, Z.-J., Du, L., Shen, X., Zheng, Y.-T., (2007) Biochem. Biophys. Res. Commun., 355, p. 1091Gupta, L., Srivastava, K., Singh, S., Puri, S.K., Chauhan, P.M.S., (2008) Bioorg. Med. Chem. Lett., 18, p. 3306Kumar, A., Katiyar, S.B., Gupta, S., Chauhan, P.M.S., (2006) Eur. J. Med. Chem., 41, p. 106Rivas, P., Cassels, B.K., Morello, A., Repetto, Y., (1999) Comp. Biochem. Physiol. C, 122, p. 27Zheng, L., Chen, H., Han, X., Lin, W., Yan, X., (2005) World J. Microbiol. Biotechnol., 21, p. 201Guan, H., Chen, H., Peng, W., Ma, Y., Cao, R., Liu, X., Xu, A., (2006) Eur. J. Med. Chem., 41, p. 1167Wu, Q., Cao, R., Feng, M., Guan, X., Ma, C., Liu, J., Song, H., Peng, W., (2008) Eur. J. Med. Chem., , 10.1016/j.ejmech.2008.03.030Shen, Y.-C., Chen, C.-Y., Hsieh, P.-W., Duh, C.-y., Lin, Y.-M., Ko, C.-L., (2005) Chem. Pharm. Bull., 53, p. 32Cao, R., Peng, W., Chen, H., Hou, X., Guan, H., Chen, Q., Ma, Y., Xu, A., (2005) Eur. J. Med. Chem., 40, p. 249Ishida, J., Wang, H.-K., Bastow, K.F., Hu, C.-Q., Lee, K.-H., (1999) Bioorg. Med. Chem. Lett., 9, p. 3319Cao, R., Chen, H., Ma, Y., Hou, X., Guan, H., Liu, X., Xu, A., (2005) Eur. J. Med. Chem., 40, p. 991Cao, R., Chen, Q., Hou, X., Chen, H., Guan, H., Ma, Y., Peng, W., Xu, A., (2004) Bioorg. Med. Chem., 12, p. 4613Zhao, M., Bi, L., Wang, W., Wang, C., Baudy-Floc'h, M., Ju, J., Peng, S., (2006) Bioorg. Med. Chem., 14, p. 6998Cao, R., Peng, W., Chen, H., Ma, Y., Liu, X., Hou, X., Guan, H., Xu, A., (2005) Biochem. Biophys. Res. Commun., 338, p. 1557Boursereau, Y., Coldham, I., (2004) Bioorg. Med. Chem. Lett., 14, p. 5841Xiao, S., Lin, W., Wang, C., Yang, M., (2001) Bioorg. Med. Chem. Lett., 11, p. 437Deveau, A.M., Labroli, M.A., Dieckhaus, C.M., Barthen, M.T., Smith, K.S., Macdonald, T.L., (2001) Bioorg. Med. Chem. Lett., 11, p. 1251Song, Y., Kesuma, D., Wang, J., Deng, Y., Duan, J., Wang, J.H., Qi, R.Z., (2004) Biochem. Biophys. Res. Commun., 317, p. 128Song, Y., Wang, J., Teng, S.F., Kesuma, D., Deng, Y., Duan, J., Wang, J.H., Sim, M.M., (2002) Bioorg. Med. Chem. Lett., 12, p. 1129Castro, A.C., Dang, L.C., Soucy, F., Grenier, L., Mazdiyasni, H., Hottelet, M., Parent, L., Adams, J., (2003) Bioorg. Med. Chem. Lett., 13, p. 2419Holla, B.S., Poojary, K.N., Rao, B.S., Shivananda, M.K., (2002) Eur. J. Med. Chem., 37, p. 511Al-Soud, Y.A., Al-Masoudi, N.A., Ferwanah, A.E.-R.S., (2003) Bioorg. Med. Chem., 11, p. 1701Demirbas, N., Karaoglu, S.A., Demirbas, A., Sancak, K., (2004) Eur. J. Med. Chem., 39, p. 793Aboraia, A.S., Abdel-Rahman, H.M., Mahfouz, N.M., EL-Gendy, M.A., (2006) Bioorg. Med. Chem., 14, p. 1236Tan, T.M.C., Chen, H., Kong, K.H., Bai, J., Li, Y., Lim, S.G., Ang, T.H., Lam, Y., (2006) Antiviral Res., 71, p. 7Amir, M., Shikha, K., (2004) Eur. J. Med. Chem., 39, p. 535Khalil, N.S.A.M., (2006) Carbohydr. Res., 341, p. 2187Wu, J., Liu, X., Cheng, X., Cao, Y., Wang, D., Li, Z., Xu, W., Clercq, E.D., (2007) Molecules, 12, p. 2003Monks, A.D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Boyd, M., (1991) J. Natl. Cancer Inst., 83, p. 75

Synthesis And Antitumor Activity Of β-carboline 3-(substituted- Carbohydrazide) Derivatives

A series of β-carboline derivatives bearing a substituted- carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The b-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N 9-methylation of b-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidenecarbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC 50 less than 10 μMfor six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC 50 = 0.04 lM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay. © 2011 Elsevier Ltd. 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