ABSTRACT
A large number of quinones have been associated with antitumor, antibacterial, antimalarial, and antifungal activities. Results of previous studies of 5-methoxy-3,4-dehydroxanthomegnin, a naphthoquinone isolated from Paepalanthus latipes Silveira, Eriocaulaceae, revealed antitumor, antibacterial, immunomodulatory, and antioxidant activities. In this study, we assessed the mutagenicity and metabolism-mediated cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin by using the Ames test and a microculture neutral red assay incorporating an S9 fraction (hepatic microsomal fraction and cofactors), respectively. We also evaluated the mutagenic activity in Salmonella typhimurium strains TA100, TA98, TA102, and TA97a, as well as the cytotoxic effect on McCoy cells with and without metabolic activation in both tests. Results indicated that naphthoquinone does not cause mutations by substitution or by addition and deletion of bases in the deoxyribonucleic acid sequence with and without metabolic activation. As previously demonstrated, the in vitro cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin to McCoy cells showed a significant cytotoxic index (CI50) of 11.9 μg/ml. This index was not altered by addition of the S9 fraction, indicating that the S9 mixture failed to metabolically modify the compound. Our results, allied with more specific biological assays in the future, would contribute to the safe use of 5-methoxy-3,4-dehydroxanthomegnin, compound that has showed in previous studies beneficial properties as a potential anticancer drug.
ABSTRACT
Helicobacter pylori is a bacterium recognized as the major cause of chronic gastritis and peptic ulcers. Infection by H. pylori induces inflammatory responses and pathological changes in the gastric microenvironment. The host Keywords: immune cells (especially neutrophils) release inflammatory mediators and large 5-methoxy-3,4-dehydroxanthomegnin amounts of reactive oxygen species (ROS), which are associated with an increased Helicobacter pyloririsk of developing gastric cancer. In this study, we evaluated the anti-H. pylori and oxidative burst antioxidantactivitiesofa1,4-naphthoquinone-5-methoxy-3,4-dehydroxanthomegnin. Paepalanthus latipes The antimicrobial activity was assessed using a spectrophotometric microdilution technique, and antioxidant activity was assessed by noting the effect of 5-methoxy3,4-dehydroxanthomegnin on the neutrophil oxidative burst using luminol-and lucigenin-amplified chemiluminescence. The results showed that 5-methoxy-3,4dehydroxanthomegnin is a potent anti-H. pylori compound (MIC 64 µg/mL and MBC 128 µg/mL) and a strong antioxidant. 5-Methoxy-3,4-dehydroxanthomegnin decreased luminol- and lucigenin-amplified chemiluminescence, with ED50 values of 1.58±0.09 µg/mL and 5.4±0.15 µg/mL, respectively, reflecting an inhibitory effect on the oxidative burst. These results indicate that 5-methoxy-3,4-dehydroxanthomegnin is a promising compound for the prevention and treatment of diseases caused by H. pylori infection, such as gastritis, peptic ulceration, and gastric cancer, because reactive oxygen intermediates are involved in the pathogenesis of gastric mucosal injury induced by H. pylori infections.
ABSTRACT
Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2) and its immunomodulatory effect on nitric oxide (NO) production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9 percent) and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively). These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.