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ABSTRACT: A phytochemical study of the ethyl acetate fractions from the partition of seeds and roots methanol extracts of Cenchrus echinatus L. led to the isolation of three resveratrol-derived stilbenoids: pallidol (1), carasiphenol C (2) and nepalensinol B (3). The results of a topic anti-inflammatory evaluation, DPPH assay and antiproliferative activity against adenocarcinoma cells (Caco 2) are described.
Natural product research 01/2012; 26(9):865-8. · 1.01 Impact Factor
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Camila Mareco Bento Leite Silva,
Francielle Pelegrin Garcia,
Jean Henrique da Silva Rodrigues,
Celso Vataru Nakamura,
Tania Ueda-Nakamura,
Emerson Meyer,
Ana Lucia Tasca Gois Ruiz,
Mary Ann Foglio,
João Ernesto de Carvalho,
Willian Ferreira da Costa, Maria Helena Sarragiotto
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ABSTRACT: A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC(50) values in the range of 1.15-8.46 µM for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC(50) in the range of 0.4 to 16.70 µM.
Chemical & pharmaceutical bulletin 01/2012; 60(11):1372-9. · 1.70 Impact Factor
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ABSTRACT: American trypanosomiasis, or Chagas' disease, is caused by Trypanosoma cruzi and affects around 15 million people throughout the American continent. The available treatment is based on two nitroheterocyclic drugs, nifurtimox and benznidazole, both only partially effective and toxic. In this context, new drugs must be found. In our previous work, the tetrahydro-β-carboline compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide, named C4, showed a potent in vitro trypanocidal effect. The goal of this study was to evaluate the in vitro and in vivo trypanocidal effects of the compound C4 associated with other drugs (benznidazole, ketoconazole, and amphotericin B). For this, we used the checkerboard technique to analyze the effect of combinations of C4 reference drugs. C4 was assayed in a murine model alone as well as in association with benznidazole. We also evaluated the parasitemia, mortality, weight, and presence of amastigote nests in cardiac tissue. A synergic effect of C4 plus benznidazole against epimastigote and trypomastigote forms was observed in vitro, and in the murine model, we observed a substantial reduction in parasitemia levels and lowered mortality rates. These findings encourage supplementary investigations of carboline compounds as potential new trypanocidal drugs.
Antimicrobial Agents and Chemotherapy 01/2012; 56(1):507-12. · 4.84 Impact Factor
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ABSTRACT: In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β-carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4-methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC50 values of 0.48, 1.50 and 1.07 µM, respectively. An in silico study of the ADME properties of the novel synthesized β-carboline derivatives was also performed.
Molecules 01/2012; 17(5):6100-13. · 2.39 Impact Factor
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ABSTRACT: 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 β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 μM for 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 μM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.
Bioorganic & medicinal chemistry 09/2011; 19(21):6400-8. · 2.82 Impact Factor
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ABSTRACT: The methanol crude extract of the leaves of Ficus radicans Roxb. 'Variegata' (Moraceae) and the n-hexane, ethyl acetate and aqueous methanol fractions resulting from its fractionation were evaluated for their anti-inflammatory, molluscicidal and free-radical scavenging activities. The crude extract and fractions exhibited significant inhibition of inflammation in both croton oil (CO)-induced ear oedema in mice (p<0.001) and carrageenan-induced rat paw oedema models (p<0.01). The molluscicidal assay against Biomphalaria glabrata showed a weak activity for the n-hexane fraction (DL(50)= 400 µg mL(-1)). A moderated 1,1-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity was observed for the ethyl acetate fraction (IC(50)= 66.2 µg mL(-1)). Fractionation of the extracts through chromatographic methods afforded the coumarins 7-methoxycoumarin, 7-hydroxy-6-methoxycoumarin and methoxy-3,4-dihydrocoumarin, the steroids β-sitosterol and β-sitosterol 3-O-β-glucopyranoside, as well as a cinnamic acid derivative and a flavonoid identified as trans-4-methoxy-2-β-D-glucopyranosyloxy cinnamic acid and quercetin 3-O-β-D-xylopyranosyl-(1 → 2)-α-L-rhamnopyranoside, respectively. The compounds were identified on the basis of their NMR spectral data and comparison with those previously reported in the literature.
Natural product research 01/2011; 26(4):323-30. · 1.01 Impact Factor
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ABSTRACT: A series of 1-phenylsubstituted beta-carbolines containing an N-butylcarboxamide group at C-3 of beta-carboline nucleus were synthesized and evaluated in vitro against epimastigote form of Trypanosoma cruzi and promastigote form of Leishmania amazonensis. Among all compounds tested, two derivatives (2b and 2d) presented potent activity against both parasites. The most active derivative 2b showed also the higher selectivity index ratio (SI) for L. amazonensis (SI=2,084). The effect of other N-alkylcarboxamide groups at C-3, such as pyrrolidyl, N-cyclohexil and N-benzylcarboxamide on T. cruzi and L. amazonensis activity was also evaluated. Our results pointed the synthesized beta-carboline-3-carboxamide derivatives as potential compounds for new drugs for Chagas' disease and leishmaniasis' treatment.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2010; 64(6):386-9. · 2.24 Impact Factor
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ABSTRACT: Com o propósito de aumentar a atividade anticâncer demonstrada anteriormente pelas 1-fenilssubstituído-3-(2-tioxo-1,3,4-oxadiazol-5-il) b-carbolinas 1a-c, neste trabalho foram realizadas a síntese e a avaliação in vitro da atividade antitumoral de novas bases de Mannich 2-7(a-c), derivadas da introdução de diferentes grupos alquilamino(metil) na unidade 1,3,4-oxadiazol de 1a-c. Os derivados 1a-c e 2-7(a-c) foram também avaliados quanto às atividades antibacteriana e antifúngica. Adicionalmente, um estudo in silico das propriedades de ADME dos novos compostos sintetizados 2-7(a-c) foi realizado pela avaliação de seus parâmetros de Lipinski e de dados de área de superfície topológica polar (TPSA) e de porcentagem de absorção (% ABS). With the purpose of activity enhancement of 1-substituted phenyl-3-(2-thioxo-1,3,4-oxadiazol-5-yl) b-carbolines 1a-c, reported as potential antitumor agents in our previous study, herein we report the synthesis and antitumor activity evaluation of several novel Mannich bases 2-7(a-c), by the introduction of different alkylamino(methyl) groups in the 1,3,4-oxadiazole unity of 1a-c. The antimicrobial activities of 1a-c and of 2-7(a-c) were also evaluated. Additionally, an in silico study of the ADME properties of novel synthesized b-carboline derivatives 2-7(a-c) was performed by evaluation of their Lipinski's parameters and topological polar surface area (TPSA) and percentage of absorption (% ABS) data.
Article J. Braz. Chem. Soc. 01/2010; 21:288-298.
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ABSTRACT: Several novel 1,3-disubstituted beta-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity against both vaccinal poliovirus and HSV-1 virus. Compound 10 presented the highest selectivity index (SI=2446.8) against HSV-1 virus and low cytotoxicity (CC(50)=1150.0+/-67.3 microM). The virus yield inhibition assay showed that compound 10 was able to inhibit HSV-1 plaque formation before and during the virus adsorption. The characteristic small plaque pattern observed in compound-treated cells suggested that compound 10 inhibited viral dissemination to neighboring cells. A computational study for prediction of ADME properties of the novel synthesized beta-carbolines derivatives was performed by determination of lipophilicity, topological polar surface area (TPSA), absorption (% ABS) and simple molecular descriptors, using Lipinski's rule.
European journal of medicinal chemistry 08/2009; 44(11):4695-701. · 3.27 Impact Factor
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ABSTRACT: Several beta-carboline compounds were evaluated for in vitro trypanocidal activity against Trypanosoma cruzi and their potential toxic effects was also assessed. beta-Carboline derivative 4 showed good activity against epimastigote, trypomastigote, and amastigote forms of T. cruzi, with a dose-dependent inhibitory effect. It showed an IC(50) of 14.9 microM against the epimastigote form and an EC(50) of 45 microM and 33 microM against trypomastigote and amastigote forms, respectively. Additionally, 4 was able to be active on mammalian cell-protozoan interaction, reducing the number of infected cells and the number of internalized parasites. The compound showed low cytotoxicity, with a selective index 31 times higher to the parasite than for mammalian cells. In human red-blood cells beta-Carboline 4 at 14.9 microM not caused haemolysis. Observed at electron microscopy 4-treated epimastigotes showed abnormal swelling of the mitochondrion, a diffuse kinetoplast, and distortions of the parasite cell body. The present data support the potential effect of this class of compounds against T. cruzi and encourage further experiments in vitro to evaluate the action mechanism of this drug and also with in vivo models.
Acta tropica 12/2008; 110(1):7-14. · 2.22 Impact Factor
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ABSTRACT: Ethanol extracts from the leaves of Cayaponia podantha. Cogn. (Cucurbitaceae), Nectandra falcifolia. (Nees) Castiglioni (Lauraceae), and Paullinia elegans. Cambess. (Sapindaceae), as well as from the aerial parts of Helicteres gardneriana. St. Hil. & Naud. (Sterculiaceae) and Melochia arenosa. Benth. (Sterculiaceae), all naturally occurring species in the Brazilian part of the Upper Paraná River and all belonging to genera used in folk medicine, were screened for anti-inflammatory activity using the carrageenan-induced pleurisy model in rats, and for antimicrobial activity using a broth microdilution assay against Staphylococcus aureus., Bacillus subtilis., Escherichia coli., Pseudomonas aeruginosa., Candida albicans., C. krusei., C. parapsilosis., and C. tropicalis.. In the analysis of anti-inflammatory activity, a 500 mg/kg body weight dose of the extracts of C. podantha., N. falcifolia., P. elegans., and H. gardneriana., administered orally (by gavage), reduced the volume of the inflammatory exudates in rats induced by intrapleural injection. H. gardneriana. also inhibited migration of leukocytes to the lesion site. Crude extract of M. arenosa. was ineffective on the intensity of the inflammatory response. Regarding antimicrobial activity, the best results were obtained with N. falcifolia. and M. arenosa. against the Gram-positive bacteria tested. N. falcifolia. was active against B. subtilis. with a minimum inhibitory concentration (MIC) of 39 µg/ml and a minimum bactericidal concentration (MBC) of 75 µg/ml and M. arenosa. with MIC of 625 µg/ml against B. subtilis. and MIC and MBC of 625 µg/ml against S. aureus.. The results obtained demonstrate the importance of pharmacological studies with neotropical plants, and further research into the specific components responsible for the observed bioactivities is under way.
10/2008; 44(7):516-521.
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ABSTRACT: Several novel 1-substituted-phenyl beta-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 microM) for all eight different types of human cancer cell lines tested. The beta-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) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), 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.
Bioorganic & medicinal chemistry 10/2008; 16(22):9660-7. · 2.82 Impact Factor
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ABSTRACT: The cis and trans isomers of methyl 1-(m-nitro)phenyl and 1-(p-nitro)phenyl-1,2,3,4-tetrahydro-9H-beta-carboline-3-carboxylates (compounds 3a,b, 4a and b) were synthesized and evaluated in vitro against epimastigote forms of Trypanosoma cruzi. Among all of the evaluated tetrahydro-beta-carboline derivatives, the compound trans-methyl 1-(m-nitro)phenyl-1,2,3,4-9H-tetrahydro-beta-carboline-3-carboxylate (3b) was found to exhibit significant trypanocidal activity (IC(50)=22.2 microM). Theoretical studies of molecular conformations and electronic properties for the synthesized compounds and benznidazole, as well as, the cyclic voltammetric (CV) behaviors' determination were performed. A comparative study of the trypanocidal activity of the nitrophenyl-tetrahydro-beta-carbolines derivatives and benznidazole, using the results of theoretical calculations and of the cyclic voltammetry experiments, is presented.
European journal of medicinal chemistry 05/2008; 44(4):1745-50. · 3.27 Impact Factor
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ABSTRACT: The known oxadiazoles 3,5-bis-(phenyl)-1,2,4-oxadiazole (3a); the 3-(4-chlorophenyl)-5-phenyl-1,2,4-oxadiazole (3b); and the new 3,5-diphenylchlorinated-1,2,4-oxadiazoles 3c-e were synthesized from the reaction of benzamidoximes with an appropriated acid chloride and cyclisation of the resulting O-acylbenzamidoxime intermediate. The compounds synthesized were characterized on the basis of their IR, NMR (1D and 2D) and mass spectral data. Compounds 3a-e were evaluated for their antimicrobial activity and for their toxicity towards brineshrimp (Artemia salina Leach).
Os oxadiazóis 3,5-bis-(fenil)-1,2,4- oxadiazol (3a) e 3-(4-clorofenil)-5-fenil-1,2,4-oxadiazol (3b), já descritos na literatura, e, os 1,2,4- oxadiazóis-3,5-fenilclorados inéditos 3c-e, foram sintetizados pela reação de bezamidoximas com um cloreto de ácido apropriado, seguido da ciclização do intermediário O-acilíco resultante. Os compostos obtidos foram caracterizados com base nas análises dos dados espectroscópicos de IV, EM e RMN (uni- e bidimensionais). Os compostos 3a-e foram submetidos a bioensaios paraavaliação de atividade antimicrobiana e, de toxicidade frente ao microcrustáceo Artemia salina Leach.
Acta Scientiarum : Technology. 01/2005;
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ABSTRACT: Two new monoterpene indole alkaloids, named croceaines A (1) and B (2), were isolated from the leaves of Palicourea crocea. The structures of 1 and 2 were elucidated by means of spectroscopic methods.
Journal of Natural Products 12/2004; 67(11):1886-8. · 3.13 Impact Factor
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ABSTRACT: Ethanolic crude extracts from the roots of Chaptalia nutans, traditionally used in Brazilian folk medicine, were screened against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa by using the disk diffusion test technique. S. aureus with 14 mm inhibition zone was considered susceptible. E. coli and P. aeruginosa without such a zone were considered resistant. As a result of this finding, the ethanolic crude extract was fractionated on silica gel column chromatography into five fractions. The ethyl acetate fraction was active against S. aureus and Bacillus subtilis. Further column chromatography separation of the ethyl acetate fraction afforded 30 fractions, which were assayed against S. aureus. Fractions 16 and 17 showed inhibition zones with S. aureus, indicating the presence of active compounds, and were subjected to purification by repeated preparative thin layer chromatography. The pure compound 7-O-beta-D-glucopyranosyl-nutanocoumarin inhibited B. subtilis and S. aureus at concentrations of 62.5 g/ml and 125 g/ml, respectively. The antibacterial property of C. nutans appears to have justified its use for the treatment of wounds, which are contaminated through bacterial infections.
Memórias do Instituto Oswaldo Cruz 04/2003; 98(2):283-6. · 2.15 Impact Factor
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ABSTRACT: Ethanolic crude extracts from the roots of Chaptalia nutans , traditionally used in Brazilian folk medicine, were screened against Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa by using the disk diffusion test technique. S. aureus with 14 mm inhibition zone was considered susceptible. E. coli and P. aeruginosa without such a zone were considered resistant. As a result of this finding, the ethanolic crude extract was fractionated on silica gel column chromatography into five fractions. The ethyl acetate fraction was active against S. aureus and Bacillus subtilis . Further column chromatography separation of the ethyl acetate fraction afforded 30 fractions, which were assayed against S. aureus . Fractions 16 and 17 showed inhibition zones with S. aureus , indicating the presence of active compounds, and were subjected to purification by repeated preparative thin layer chromatography. The pure compound 7-O- β -D-glucopyranosyl-nutanocoumarin inhibited B. subtilis and S. aureus at concentrations of 62.5 µ g/ml and 125 µ g/ml, respectively. The antibacterial property of C. nutans appears to have justified its use for the treatment of wounds, which are contaminated through bacterial infections.
Memórias do Instituto Oswaldo Cruz (ISSN: 1678-8060) Vol 98 Num 2.
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ABSTRACT: Several novel 1,3-disubstituted β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity against both vaccinal poliovirus and HSV-1 virus. Compound 10 presented the highest selectivity index (SI = 2446.8) against HSV-1 virus and low cytotoxicity (CC50 = 1150.0 ± 67.3 μM). The virus yield inhibition assay showed that compound 10 was able to inhibit HSV-1 plaque formation before and during the virus adsorption. The characteristic small plaque pattern observed in compound-treated cells suggested that compound 10 inhibited viral dissemination to neighboring cells. A computational study for prediction of ADME properties of the novel synthesized β-carbolines derivatives was performed by determination of lipophilicity, topological polar surface area (TPSA), absorption (% ABS) and simple molecular descriptors, using Lipinski′s rule.Graphical abstractNovel b-carboline derivatives containing a substituted carbohydrazide group at C-3 were prepared and identified as antiviral agents against herpes simplex virus type 1 (HSV-1) and vaccinal poliovirus (VP), at non-cytotoxic concentrations.
European Journal of Medicinal Chemistry. 44(11):4695-4701.
