RESUMO
Methoxy polyethylene glycol conjugated with coenzyme Q10 (mPEG)-CoQ10 and analog adducts with amino acids as spacers were synthesized as a new drug delivery systems for CoQ10. Alanine and branched chain amino acids (valine, leucine and isoleucine) were conjugated to mPEG by an amide linkage and to CoQ10 by an ester bond. Recently, branched chain amino acids (BCAAs), which are released along with CoQ10, have received increasing attention as 'anti-fatigue' elements. FT-IR and 1H NMR spectroscopic analysis were useful to characterize the synthesized conjugates. Studies in vitro, in buffer solutions at different pH and in the presence of esterase were conducted. The hydrolysis studies showed a specific cleavage dependent on the pH of the medium and by the presence of proteolytic enzymes. The results showed the improvement of the pharmacokinetic properties of CoQ10. The antioxidant activity of the synthesized conjugates was also evaluated by DPPH assay.
Assuntos
Antioxidantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Ubiquinona/análogos & derivados , Aminoácidos/química , Antioxidantes/química , Antioxidantes/farmacocinética , Liberação Controlada de Fármacos , Esterases/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Ubiquinona/administração & dosagem , Ubiquinona/química , Ubiquinona/farmacocinéticaRESUMO
Infections caused by non-tuberculous mycobacteria and multidrug-resistant Mycobacterium tuberculosis are difficult to treat, and so new compounds potentially active against these bacteria are being sought. A series of 2-pyridinecarboxamidrazone derivatives, recently synthesized, have been evaluated for their inhibitory activity against 17 Mycobacterium avium isolates; the agar dilution method showed different degrees of susceptibility to the new molecules. Four molecules, three of which are chlorine derivatives, inhibited 94% of the strains tested with an MIC of 32 mg/L. These data indicate that these new pyridine-2-carboxamidrazones merit further study as antimycobacterial agents.
Assuntos
Antibióticos Antituberculose/farmacologia , Mycobacterium avium/efeitos dos fármacos , Piridinas/farmacologia , Antibióticos Antituberculose/química , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium avium/isolamento & purificação , Piridinas/químicaRESUMO
[5-(Pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed a feable activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.
Assuntos
Antibacterianos/síntese química , Tiadiazóis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Mycobacterium/efeitos dos fármacos , Relação Estrutura-Atividade , Tiadiazóis/química , Tiadiazóis/farmacologiaRESUMO
5-Aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1H-pyrazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. The compounds showed an interesting activity against a strain of Mycobacterium tuberculosis and a human strain of M. tuberculosis H4.
Assuntos
Antibacterianos/síntese química , Antituberculosos/síntese química , Pirazóis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antituberculosos/química , Antituberculosos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Pirazóis/química , Pirazóis/farmacologia , Relação Estrutura-AtividadeRESUMO
6-[(Arylmethylenamino)carbonyl]-3-(pyridin-2-yl)-4H-1,2,4-triazin-5-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis.
Assuntos
Antituberculosos/farmacologia , Triazinas/farmacologia , Antituberculosos/síntese química , Antituberculosos/química , Estrutura Molecular , Mycobacterium avium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Triazinas/síntese química , Triazinas/químicaRESUMO
N1-[1-[3-aryl-1-(pyridin-2,3-, and 4-yl)-3-oxo[propyl]-2- pyridinecarboxamidrazone derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.
Assuntos
Antibacterianos/farmacologia , Mycobacterium avium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Piridinas/síntese química , Piridinas/farmacologia , Testes de Sensibilidade Microbiana , Piridinas/química , Análise EspectralRESUMO
A series of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone derivatives containing the indole moiety was prepared. Some of the synthesized compounds showed an interesting in vitro antimycobacterial activity against a strain of Mycobacterium tuberculosis.
Assuntos
Antituberculosos/síntese química , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
A series of 5-substituted 2-arylamino-1,3,4-thiadiazole derivatives was prepared. The antimicrobial activity of these compounds against some strains of bacteria and a strain of Candida albicans was determined, together with that of the corresponding thiosemicarbazone derivatives, which are intermediates in the synthetical procedure.
Assuntos
Anti-Infecciosos/síntese química , Bactérias/efeitos dos fármacos , Tiadiazóis/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Tiadiazóis/farmacologiaRESUMO
After preliminary in vitro screening of 15 newly synthesized compounds belonging to the chemical class of N1-(aryliden)-4-pyridinecarboxyamidrazones against Mycobacterium tuberculosis reference strain H37 Rv, we determined the minimum inhibitory concentrations (MICs) of the six most promising chemicals against different species of Mycobacterium and different strains of M. tuberculosis. The agar dilution method was employed against M. gordonae, M. bovis, M. kansasi, M. avium, M. fortuitum and on eighteen different strains of M. tuberculosis, isolated from human bronchial aspirates. The results obtained confirmed that the newly synthesized chemicals possessed a very interesting antitubercular activity, their MICs ranging from 4 micrograms/ml to 16 micrograms/ml.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Piridinas/farmacologia , Antituberculosos/química , Antituberculosos/classificação , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/classificação , Piridinas/química , Especificidade da EspécieRESUMO
A series of N1-aryliden-4-pyridinecarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis.
Assuntos
Mycobacterium/efeitos dos fármacos , Piridinas/síntese química , Antituberculosos/síntese química , Antituberculosos/farmacologia , Resistência Microbiana a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium avium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Piridinas/farmacologiaRESUMO
A series of N1-aryliden-2-pyridincarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis.
Assuntos
Antibacterianos/síntese química , Mycobacterium/efeitos dos fármacos , Piridinas/síntese química , Antibacterianos/farmacologia , Antituberculosos/síntese química , Antituberculosos/farmacologia , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Piridinas/farmacologia , Relação Estrutura-AtividadeRESUMO
A rapid, sensitive and specific reversed phase HPLC method for the simultaneous assay of amiodarone and its major metabolite desethylamiodarone in human serum has been developed. This method is suitable for pharmacokinetic studies and for monitoring of the drug and metabolite concentrations in serum of patients on both short and long-term therapy with amiodarone.
Assuntos
Amiodarona/análogos & derivados , Amiodarona/sangue , Cromatografia Líquida de Alta Pressão , HumanosRESUMO
After preliminary in vitro screening of 17 newly synthesized compounds belonging to the chemical class of N1-(aryliden)-2-pyridinecarboxyamidrazones, active against Mycobacterium tuberculosis H37Rv, the minimum inhibitory concentrations (MICs) of the ten most promising agents against three clinical isolates were determined by agar dilution. Compounds 12 and 14 were the most active, each inhibiting strain H37Rv at concentrations of 8 microg/ml and having a MIC of 16 microg/ml against the human isolates. The results obtained in this preliminary study confirmed the interesting antitubercular properties of these newly synthesized compounds and allowed us to carry out our investigations over a large number of isolated clinical strains.
Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Piridinas/farmacologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
The synthesis and in vitro antifungal activity of some pyridincarboxyamidrazone derivatives are described. 2-pyridincarboxyamidrazone derivative (IIa) in comparison with miconazole showed an interesting even if low antimycotic activity.
Assuntos
Amidinas/farmacologia , Antifúngicos/síntese química , Piridinas/farmacologia , Amidinas/síntese química , Aspergillus niger/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Fenômenos Químicos , Química , Meios de Cultura , Fungos/efeitos dos fármacos , Furanos/síntese química , Furanos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Piridinas/síntese química , Tiofenos/síntese química , Tiofenos/farmacologia , Trichophyton/efeitos dos fármacosRESUMO
A series of 2-arylamino-1,3,4-thiadiazole derivatives was synthesized with the aim to find new antihypertensive compounds. The antihypertensive activity of some of these compounds was examined intraperitoneally in conscious spontaneously hypertensive rats (SHR). The tested compounds showed activity, but none of these possessed a higher potency than the reference substance guanabenz.
Assuntos
Anti-Hipertensivos/síntese química , Tiadiazóis/síntese química , Animais , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Químicos , Química , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos SHR , Tiadiazóis/administração & dosagem , Tiadiazóis/farmacologia , Fatores de TempoAssuntos
Anti-Hipertensivos/síntese química , Guanidinas/síntese química , Hidrazinas/síntese química , Piridinas/síntese química , Triazóis/síntese química , Animais , Pressão Sanguínea/efeitos dos fármacos , Guanidinas/farmacologia , Hidrazinas/farmacologia , Masculino , Piridinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Triazóis/farmacologiaRESUMO
The synthesis of new benzylidenaminoguanidine compounds is described. Some of these compounds were tested for antihypertensive activity in conscious unrestrained spontaneously hypertensive rats. The compounds examined possess a significant antihypertensive activity, qualitatively different from that of clonidine. For the tested compounds, the absence of the transient rise in blood pressure, which appears immediately after administration of clonidine-like drugs, is noteworthy.