RESUMO
A series of seven derivatives of 1,1'-(5,6-dimethoxy-3-methyl-1-benzofuran-2,7-diyl)diethanone was synthesized and characterized by (1)HNMR and ESI MS spectra and elemental analyses. The obtained new compounds and three halogen derivatives of benzofuran, reported in our earlier work, were tested for their cytotoxic properties in human chronic (K562) and acute (HL60) leukemia cells, human cervical cancer (HeLa), and normal endothelial cells (HUVEC). Four compounds (2, 3, 4, 5), which contain halogens in their structure showed significant anticancer activity. The most promising was 1,1'-[3- (bromomethyl)-5,6-dimethoxy-1-benzofuran-2,7-diyl]diethanone (2), which was highly and selectively toxic for K562 cells (IC50 of 5µM) and HL60 cells (IC50 of 0.1µM), which showed no cytotoxicity toward HeLa and HUVEC cells. Moreover, the observed remarkable cytotoxicity of this compound toward K562 cells resulted from cells apoptosis.
Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Halogênios/química , Halogênios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Células HL-60 , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Células K562 , Relação Estrutura-AtividadeRESUMO
The purpose of this study, the direct separation of aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which was found in earlier studies as potential anticancer drugs, were performed. Capillary electrophoresis offers the possibility of fast, cheap, and reproducible separations for compounds I and II. In this paper, the simultaneous separation of I and II by capillary zone electrophoresis has been achieved within 8 min by use of 50 mM phosphate buffer of pH 2.5. Analysis of the two compounds in the serum plasma standards was conducted. Limits of detection of I and II by UV absorbance at 200 nm were achieved in the range of 156.3-156.6 ng/mL. The method was validated for linearity, accuracy, precision, limits of detection, and quantification. The calibration equation revealed a good linear relationship (r(2) = 0.998-0.999). Sufficient recovery was observed in the range of 96.3-99.5%. The method showed good reproducibility with intra- and interday precision of 0.97 and 1.76%, respectively. The quantification limits for the compounds were in the range of 477.0-479.8 ng/mL. The proposed method was applied to the analysis of real serum samples.
Assuntos
Antineoplásicos/isolamento & purificação , Eletroforese Capilar/métodos , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Imidas/isolamento & purificação , Antineoplásicos/sangue , Compostos Heterocíclicos com 3 Anéis/sangue , Humanos , Imidas/sangue , Estrutura Molecular , Sensibilidade e EspecificidadeRESUMO
A series of arylpiperazine derivatives of 1,16-diphenyl-19-azahexacyclo-[14.5.1.02,15.03,8.09,14.017,21]docosa-2,3,5,7,8,9,11,13,14-nonaene-18,20,22-trione and 4,10-diphenyl-1H,2H,3H,5H-indeno[1,2-f]isoindole-1,3,5-trione was synthesized. The pharmacological profile of compound 4 at the 5-HT1A receptor was measured by binding assay. The title compounds were tested in cell-based assay against the human immunodeficiency virus type-1. The X-ray crystallographic studies of derivatives 2, 6, 7, 11, 19, and 20 were presented.
RESUMO
In the present paper, we describe proapoptotic activity of several heterocyclic compounds 9, 12, 18, 19 and 20 possessing succinimide (as well as succinimide related) moieties. The compounds properties were examined with the aid of flow cytometry on the promyelocytic leukemia cell line HL-60. The highest proapoptotic activity exhibited compound 12 (4-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-1,7-diethyl-8,9-diphenyl-4-azatricyklo[5.2.1.0(2,6)]-dec-8-ene-3,5,10-trione). The synthesis of compounds 1-17 is also described. The structures of obtained compounds were characterized by 1H NMR, 13C NMR, ESI MS and/or elemental analyses.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Succinimidas/farmacologia , Citometria de Fluxo , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
In the search for novel biological agents, a series of new derivatives N-substituted 1,3-benzoxazol-2(3H)-one, 5-chloro-1,3-benzoxazol-2(3H)-one, 6-bromo-1,3-benzoxazol-2(3H)-one were prepared. All of the compounds were characterized by 1H NMR, 13C NMR and ESI MS spectra. Moreover, for compound 1 an Xray structure was determined. All derivatives were tested for antimicrobial activity against a selection of Gram-positive, Gram-negative bacteria and yeasts. The selected compounds (2-8, 10) were tested for their cytotoxic properties in K562, HeLa and normal cells.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzoxazóis/síntese química , Benzoxazóis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Células HeLa , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Células K562 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Leveduras/efeitos dos fármacos , Leveduras/crescimento & desenvolvimentoRESUMO
In the search for novel antimicrobial agents, a series of new derivatives - N-substituted imides were prepared. All of the compounds were characterized by 'H NMR and ESI MS spectra. These derivatives were tested for antimicrobial activity. Microorganisms used in this study included aerobic and facultative anaerobic bacteria such as Staphylococcus aureus, Escherichia coli, Stenotrophomonas maltophilia, and obligatory anaerobes such as Bacteroides fragilis, Bacteroides thetaiotaomicron and Propionibacterium acnes. Moreover, Candida albicans yeast was used. For representatives of all species the MICs of the investigated compounds were determined. Most of investigated derivatives had no antimicrobial activity (MIC > 512 mg/L) except the derivative 22 which showed slight activity against Gram-positive aerobes and anaerobes.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Imidas/síntese química , Imidas/farmacologia , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade MicrobianaAssuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Concentração Inibidora 50 , Células K562 , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Halogen and aminoalkyl derivatives of methyl 5-methoxy-2-methyl-1-benzofuran-3-carboxylate were prepared using 5-hydroxy-2-methyl-3-benzofuranocarboxylic acid as starting material. (1)H-NMR spectra were obtained for all of the synthesized structures, and for compounds 1 and 2 X-ray crystal structures were obtained too. All derivatives were tested for antimicrobial activity against a selection of Gram-positive cocci, Gram-negative rods and yeasts.
Assuntos
Anti-Infecciosos/síntese química , Benzofuranos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Relação Estrutura-Atividade , Difração de Raios XRESUMO
Halogen derivatives of selected 3-benzofurancarboxylic acids were prepared using 6-acetyl-5-hydroxy-2-methyl-3-benzofuranocarboxylic acid as starting material. (1)H-NMR spectra were obtained for all of the synthesized structures, and for compound VI, an X-ray crystal structure was also obtained. All derivatives were tested for antimicrobial activity against a selection of Gram-positive cocci, Gram-negative rods and yeasts. Three compounds, III, IV, and VI, showed antimicrobial activity against Gram-positive bacteria (MIC 50 to 200 microg/mL). Compounds VI and III exhibited antifungal activity against the Candida strains C. albicans and C. parapsilosis (MIC-100 microg/mL).
Assuntos
Anti-Infecciosos/síntese química , Benzofuranos/farmacologia , Ácidos Carboxílicos/farmacologia , Anti-Infecciosos/farmacologia , Benzofuranos/química , Ácidos Carboxílicos/química , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Halogenação , Testes de Sensibilidade MicrobianaRESUMO
The preparation of a number of cyclic imide 5-HT(1A) receptor ligand derivatives has been described. Their structures were conformationally constrained by introducing rigid linkers containing unsaturated bonds or aromatic benzene rings. These compounds are expected to possess anxiolytic and antidepressant activity.
Assuntos
Imidas/química , Imidas/síntese química , Piperazinas/química , Piperazinas/síntese química , Receptor 5-HT1A de Serotonina/química , Ligantes , Conformação MolecularRESUMO
The preparation of a number of derivatives of N-hydroxy-1-methoxybicyclo[2.2.2]oct-5-ene-2,3-dicarboximide with an expected anxiolytic and antidepressive activity has been described.
Assuntos
Ansiolíticos/síntese química , Ansiolíticos/farmacologia , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/farmacologia , Animais , Antidepressivos/síntese química , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Injeções Intraperitoneais , Espectroscopia de Ressonância Magnética , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Espectrofotometria Infravermelho , Natação/psicologiaRESUMO
The preparation is described of a number of new N-substituted derivatives of dibenzo[e.h]bicyclo[2.2.2]octane-2,3-dicarboximide with potential anxiolytic activity.