RESUMO
Retinoids consist of a family of naturally occuring compounds including all-trans retinoic acid (ATRA), retinal, retinol (vitamin A), 9-cis retinoic acid, 13-cis retinoic acid as well as a large number of synthetic derivatives. Retinoids are known to elicit diverse pharmacological profiles such as controlling cell differentiation/proliferation and modulating specific premalignant lesions and reducing second primary tumors in patients. Clinical use of retinoids is limited due to their toxicity. Three benzimidazole retinoid derivatives (BITN, BITNm, BITNe) were synthesized and were examined in terms of genotoxicity towards human lymphocyte cultures by sister chromatid exchange (SCE) analysis. It has been found that BITN decreased the number of SCEs 20% at 10(-6) M, but had no effect at 10(-5) M. No significant effect on SCEs was observed for BITNm and BITNe at both concentrations. ATRA increased the SCEs (35%) at 10(-5) M but had no effect at 10(-6) M. The results have shown that benzimidazole retinoids did not induce SCE significantly. Besides this, BITN reduced the SCEs and had a protective effect at low concentration. Since the induction of glutathione S-transferase (GST) is associated with anticancer drug resistance, the effects of BITN, BITNm, BITNe and ATRA on human lymphocyte GSTs were also investigated using CDNB as substrate. BITN and BITNm induced GST activities 54% and 49% respectively at 10(-5) M, but had no effect at 10(-6) M. BITNe induced GST activity 62% at 10(-5) M and 35% at 10(-6) M. ATRA had no effect on GST activity at 10(-5) M.
Assuntos
Benzimidazóis/toxicidade , Mutagênicos , Retinoides/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Compostos de Diazônio/metabolismo , Relação Dose-Resposta a Droga , Glutationa Transferase/genética , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/enzimologia , Troca de Cromátide Irmã/efeitos dos fármacosRESUMO
The synthesis and lipid peroxidation (LP) inhibition activity of several novel indole melatonin analogues are reported. Compounds have shown variable antioxidant features depending on the substitution pattern. Melatonin and the antioxidant reference compound butyl hydroxy toluen (BHT) were used to compare the antioxidant capability of the compounds synthesized.
Assuntos
Antioxidantes/síntese química , Etilaminas/síntese química , Indóis/síntese química , Melatonina/análogos & derivados , Melatonina/síntese química , Acilação , Animais , Antioxidantes/química , Etilaminas/química , Indicadores e Reagentes , Indóis/química , Peroxidação de Lipídeos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Triptaminas/síntese químicaRESUMO
Some biologically important and melatonin-related indole-3-propionamide derivatives were synthesized. The compounds synthesized were analyzed and characterized first by NMR and mass spectrometry and then investigated by analytical voltammetric techniques. Based on this study a simple, rapid and sensitive voltammetric method was developed for the determination of the indole derivatives that are readily oxidized at the carbon-based electrodes. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode. The characteristics of the corresponding electrode reaction were discussed.
