RESUMO
Ten 2-aryl or heteroaryl-3-nitrosoimidazo[1,2-a]pyridine derivatives were synthesised as potential antiretroviral agents. The new compounds were characterized by elemental analysis, 1H NMR, and by crystallography for (14). The compounds were devoid of any activity against HIV-1 or HIV-2.
Assuntos
Fármacos Anti-HIV/síntese química , Antivirais/síntese química , Imidazóis/síntese química , Imidazóis/farmacologia , Compostos Nitrosos/síntese química , Compostos Nitrosos/farmacologia , Piridinas/síntese química , Piridinas/farmacologia , Retroviridae/efeitos dos fármacos , Células Cultivadas , Cristalografia por Raios X , Humanos , Espectroscopia de Ressonância MagnéticaRESUMO
The synthesis and antiviral activity of original dibromoimidazo[1,2-a]pyridines bearing a thioether side chain are reported. Molecular modeling was used to identify biophoric structural patterns that are common to 16 compounds. Structure-activity relationship (SAR) studies identified hydrophobicity (logP) as the most important factor for activity. From these SAR studies, the antiviral activity could be predicted.
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Piridinas/síntese química , Piridinas/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Células Gigantes/efeitos dos fármacos , Células Gigantes/virologia , HIV-1/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Relação Quantitativa Estrutura-AtividadeRESUMO
This work reports the synthesis and the antiviral activities of 3-benzamido, 3-phenylureido and 3-phenylthioureido derivatives in the imidazo[1,2-a]pyridine series. The structure was proven by NMR spectroscopy. The synthesized compounds were evaluated against a large number of viruses. The 3-phenylthioureido derivative 7 showed moderate activity against human cytomegalovirus (HCMV) in vitro. The crystallographic data for 8 are also reported and explain the absence of activity against human immunodeficiency virus (HIV).
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Compostos de Fenilureia/síntese química , Compostos de Fenilureia/farmacologia , Tioureia/análogos & derivados , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Células Cultivadas , Cristalografia por Raios X , Citomegalovirus/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Relação Estrutura-Atividade , Tioureia/síntese química , Tioureia/farmacologia , Ensaio de Placa ViralRESUMO
From the latex of Lapsana communis L. subps. communis, five guaianolide glycosides were identified: crepiside E, tectoroside and three new ones: 3-O-beta-D-glucopyranosyl-8-O-beta-acetyl-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-4(15),10(14),11(13)-triene-6,12-olide, 3-O-beta-D-glucopyranosyl-8-O-beta-acetyl-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-3(4),10(14), 11(13)-triene-15-methyl-6,12-olide, and 3-O-beta-glucopyranosyl-8-O-beta-(4-hydroxyphenyl)-lactyl-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-3(4),10(14),11(13)-triene-15-methyl-6,12-olide. Their structures were established by spectroscopic methods.
Assuntos
Asteraceae/química , Glicosídeos/isolamento & purificação , Lactonas/química , Sesquiterpenos/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/farmacologia , Leucemia L1210/patologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
The anticancer activity of 4-methylaminopyridol[1,2-e]purine 6a, 4-(piperidin-1-yl)pyrido[1,2-e]purine 7a and their 7-methyl derivatives 6b, 7b was investigated against the human MCF7 cancer cell line in vitro. The sensitive cell line showed a range of sensitivities to 6a, 6b, 7a, 7b (IC50: 1.6 to 7.2 x 10(-4) M) and sensitivity to doxorubicin (IC50: 7.5 x 10(-7) M). A resistant cell line with the multidrug resistant phenotype was sensitive to these derivatives (IC50: 1.8 to 6.7 x 10(-4) M), doxorubicin (IC50: 5 x 10(-5) M) and drug activity seems to be not affected by MDR resistance. Our data show that 6a, 6b, 7a and 7b appear to exert a low cytotoxicity on sensitive and MDR resistant MCF7 human cancer cell lines.