Applied biological and physicochemical activity of isoquinoline alkaloids: oxoisoaporphine and boldine.

The aim of this study was to determine the electronic influence of substituent groups and annelated rings such as oxazole-oxazinone on the physicochemical and photoprotection, antioxidant capacity, toxicity and singlet oxygen photosensitization biological properties of isoquinoline alkaloid frameworks. Thus, oxoisoaporphine derivatives 1-5 and 3-azaoxoisoaporphine (6), some of them with phenolic structures, did not present any antioxidant capacity, possibly either by formation of keto-enol tautomerism species or the formation of unstable free radicals. Due to the singlet oxygen quantum yields (FD) near to unity, and greater photostability than phenalenone, oxoisoaporphines 4-6 may be considered as photosensitizers for singlet oxygen production and can be used as new universal study tools. The biological application as antibacterial agents is an important and possible tool in the study of compounds with low cytotoxicity and high reactivity in antineoplastic chemotherapy. On the other hand, when boldine and its annelated derivatives B1-4 are irradiated, a photoprotector effect is observed (SPF = 2.35), even after 30 minutes of irradiation. They also act as photoprotectors in cell fibroblast cultures. No hemolysis was detected for boldine hydrochloride and its salts without irradiation. In solutions irradiated before incubation (at concentrations over 200 ppm) photoproducts were toxic to the nauplii of Artemia salina.

Lack of effects of 2,4-dichlorophenoxyacetic acid administration on markers of oxidative stress during early pregnancy in mice.

Induction of oxidative stress by 2,4-dichlorophenoxyacetic acid (2,4-D) both as a pure compound and in commercial formulation was investigated during early pregnancy in mice. Pregnant animals were exposed to increasing doses of the herbicide (0.01, 0.1 and 100mg/kg/d) during gestation days 0-9, after which animals were euthanized and their blood analyzed for catalase activity, thiobarbituric acid reactive substances (TBARs) and total antioxidant capacity (TAC). Number of corpora lutea and uterine implantations and resorptions were also determined. Herbicide exposure did not cause any overt signs of maternal toxicity at any of the doses administered; neither did it cause an effect on developmental parameters. Catalase activity and TBARs were not modified by herbicide exposure although TAC was significantly decreased at 100mg/kg/d of both pure and formulated compound. Thus, 2,4-D does not seem to induce oxidative stress during early pregnancy in mice at the doses administered, indicating that this mechanism is probably not involved in mediating herbicide toxicity at these dose levels. Furthermore, since no manifestations of developmental toxicity were observed after administration of the herbicide, it is also possible that 2,4-D may not produce any early developmental toxicity at the low environmentally relevant doses tested in this animal model.

Spectroscopic and photochemical properties of the lichen compound lobaric acid.

Lichens synthesize and accumulate photoprotective compounds against possible damage induced by UV radiation in the photobiont. A biological model has been recently formulated that allows the use of lichens to evaluate changes at different UV radiation levels. The thermodynamics, photophysical and photochemical properties of lobaric acid were studied in acetonitrile, ethanol and Brij 35(3%) micelles at different pH values. Also the sun protector factor (SPF) was determined by in vitro methods. Lobaric acid was extracted from Stereoculon alpinum Laur. and characterized by means of standard procedures. Solutions were irradiated in oxygen and under nitrogen conditions with a UV medium pressure lamp. Lobaric acid absorbs at 287, 303 nm, and no fluorescence emission was observed. The maximum value of the molar extinction coefficient (5479.6 M(-1) cm(-1)) was obtained in Brij 35 at pH 12. Solubility is pH dependant and is highest in Brij 35 at pH 12 (4.45 x 10(-4) M). Photoconsumption quantum yields ranged between 10(-4) and 10(-5) in aerobic and anaerobic experimental conditions. Lobaric acid SPF was very low (0.5) compared with homosalate (4.0), (reference solar filter). Two pKa values, 5.05 (carboxylic acid group deprotonation) and 9.75 (phenolic OH deprotonation), were determined.

Photostability and photoprotection factor of boldine and glaucine.

Boldine hydrochloride was more photounstable than boldine after irradiation with UVB (lambda = 300 nm). However, photoconsumption quantum yields, for glaucine hydrochloride (6.5 x 10(-2)) and boldine hydrochloride (6.7 x 10(-2)) in air, were quite similar. The photolysis was oxygen dependent in both cases, and the effect over the kinetics after the addition of 2,2,6,6-tetramethyl-1-piperidinyloxy suggested free radicals participation. The fact that the antioxidative capacity of boldine and boldine hydrochloride did not change during the photolysis, suggests that the phenolic structure remains unchanged in the photoproducts, corroborated with the photoproducts analysis. The photoprotection capacity was evaluated before and after irradiation. Results indicate that the values before irradiation are similar for all three compounds, only glaucine increasing its capacity with length of irradiation time.

Induced and photoinduced DNA damage by quinolones: ciprofloxacin, ofloxacin and nalidixic acid determined by comet assay.

Quinolones are degraded by light with loss of their antimicrobial activity, generating active species or radicals. Evidence exists that some fluoroquinolones (lomefloxacin, fleroxacin and enoxacin) induce damage to the cellular membrane and DNA cleavage by photosensitization. In this study, the genotoxic potential of the quinolones ofloxacin, nalidixic acid and ciprofloxacin (three antimicrobials frequently used in therapy) was evaluated upon irradiation with UV light by using the comet assay on cells of the Jurkat line. The results demonstrate that there are significant differences between the control groups (positive control with 50 microM H2O2, negative controls without drug and with and without irradiation) and the groups of irradiated quinolones (ofloxacin 2.76 x 10(-5) M, nalidixic acid 2.15 x 10(-4) M and ciprofloxacin 2.01 x 10(-5) M), indicating that, at the dose of irradiation employed (necessary to produce 50% photodegradation), the photodecomposition of the quinolones enhanced DNA damage. The unirradiated drugs also exhibited genotoxicity significantly different from that of the negative control.