In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard
in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering Duvelisib the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of ICA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral
blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA. (C) 2010 Elsevier B.V. All rights reserved.”
“Spectrophotometric this website study was carried out, for the first time, to investigate the reaction between the antidepressant fluvoxamine (FXM) and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 9), an orange-colored
product exhibiting maximum absorption peak (lambda(max)) at 470 nm was produced. The kinetics of the reaction was investigated and its activation energy was found to be 2.65 kcal mol(-1). Because of this low activation energy, the reaction proceeded easily. The stoichiometry of the reaction was determined and the reaction mechanism was postulated. This color-developing reaction was successfully employed in the find protocol development of simple and rapid spectrophotometric method for determination of FXM in its pharmaceutical dosage forms. Under the optimized reaction conditions, Beer’s law correlating the absorbance (A) with FXM concentration (C) was obeyed in the range of 0.6-8 mu g ml(-1). The regression equation for the calibration data was A=0.0086+0.1348C, with good correlation coefficient (0.9996). The molar absorptivity (epsilon) was 5.9 x 10(4) I mol(-1) cm(-1). The limits of detection and quantification were 0.2 and 0.6 mu g ml(-1), respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2%.