RESUMO
Pursuing our searches on quinolonecarboxylic acids we used a simple three-step one pot procedure to synthesize novel 1,7-disubstituted-6-nitroquinolones. The new derivatives were tested against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) as well as against both gram-positive and gram-negative bacteria. In vitro assays showed some derivatives were endowed with good inhibiting activities against tested mycobacteria. Some derivatives were also found more potent than ciprofloxacin and ofloxacin (used as reference drugs) against gram-positive bacteria.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Fluoroquinolonas/síntese química , Nitroquinolinas/síntese química , Antibacterianos/uso terapêutico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos , Química Farmacêutica/tendências , Ciprofloxacina/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Itália , Testes de Sensibilidade Microbiana/métodos , Estrutura Molecular , Complexo Mycobacterium avium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Nitroquinolinas/farmacologia , Ofloxacino/farmacologia , Relação Estrutura-AtividadeRESUMO
A new series of 3-isopropyl-, 3-trifluoromethyl- and 3-bromomethylquinoxaline-2-ones variously substituted on the benzo-moiety were synthesized and submitted to a preliminary in vitro evaluation for antibacterial, antifungal and anti-HIV activities. Furthermore, all compounds were also tested for cytotoxicity. Results of the screening showed that compound 10 exhibits moderate antimicrobial activity against Staphylococcus aureus (MIC = 33 microM), and that 25 and 26 showed interesting cytotoxicity versus mock-infected MT-4 cells. All the other compounds were inactive.
Assuntos
Anti-Infecciosos/síntese química , Antifúngicos/síntese química , Antivirais/síntese química , Quinoxalinas/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , HIV/efeitos dos fármacos , Humanos , Modelos Lineares , Testes de Sensibilidade Microbiana , Quinoxalinas/química , Quinoxalinas/farmacologia , Relação Estrutura-AtividadeRESUMO
The pyrrolo[1,2-f]phenanthridines 8-22 and the corresponding non-rigid analogues 23-41 were synthesised and their ability to inhibit the replication of HIV-1 was tested. Only the polycyclic derivatives 10, 11, and 13 showed a weak anti-HIV activity, whereas several pyrrolo-phenanthridines (8, 10, 16-18) were found to stimulate the multiplication of MT-4 cells at low concentrations. Derivative 10 demonstrated to possess the unique property of stimulating the multiplication of lymphocytes joined to HIV inhibition.
Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Fenantridinas/farmacologia , Pirróis/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Moleculares , Fenantridinas/síntese química , Fenantridinas/química , Pirróis/síntese química , Pirróis/química , Relação Estrutura-AtividadeRESUMO
In the course of a study on 1H-imidazol-1-amine derivatives as antifungal agents, we found that N-[(1,1'-biphenyl)-4-ylmethyl]-N-[(2,4-dichlorophenyl)methyl]-1H-imidazol-1-amine (1a) exhibited promising activities. In order to explore more in detail the structure-activity relationship of this new class of antifungal agents, we report now the synthesis and the biological activity of new analogues (1b-k) of compound 1a. The synthesis was performed using N-[(1,1'-biphenyl)-4-ylmethyl]-1H-imidazol-1-amine as starting material which was reacted with the proper arylmethyl halide. Most of the newly synthesized imidazolamines exhibited both fungal growth inhibition activity and cellular selectivity.