In vitro cytotoxic activity of naphtho[1,2-b]furan, furo[2,3-f], furo[2,3-g] and furo[3,2-g]quinoline derivatives.

Some naphtho[1,2-b]furan, furo[2,3-f], furo[2,3-g] and furo[3,2-g]quinoline derivatives have been submitted to in vitro cytotoxic tests towards L 1210, MDA-MB 231 and PC3 cell lines. Among them, the furoquinone structures exhibited the most interesting IC50 values.

Development of renewable surface biosensors to meet industrial needs for measurement of glucose in fruit juices.

Most biosensors reported to date have been prepared, studied and used under laboratory conditions. The feasibility of a very great number of biosensors seems to be demonstrated and their characteristics, very often, established as corresponding to the demands of the modern analysis. The operational stability of the biosensors, according to authors, is almost always acceptable. The long term storage, with analytical quality conservation that is necessary to commercialise products, has rarely been studied. The stability of biosensors has to remain not only during the fabrication step or their subsequent utilisation, but also throughout the whole commercial shelf-life of the sensor, from producer to end user, through wholesaler and/or retailer. We developed the manufacturing processes, on a large scale, of renewable surface electrodes modified with enzymes such as oxidoreductases. The process consisting of several steps is described and the analytical behaviours of resulting biosensors is studied and correlated with the effects of different constraints applied during the fabrication process.

Synthesis of furonaphth[1,3]oxazine and furo[1,3]oxazinoquinoline derivatives as precursors for an o-quinonemethide structure and potential antitumor agents.

The synthesis of dihydro furonaphth[1,3]oxazine derivatives 3 was performed through a Mannich-type condensation between 2-cyano-5-hydroxy-3-methylnaphtho[1,2]furan 2a, 1.5 eq of a primary amine and 3 eq of formaldehyde. Similarly, 2-cyano-5-hydroxy-3-methylfuro[2,3-f]quinoline 2b gave the dihydro furo[1,3]oxazino-quinoline compounds 4. Heating a mixture of the naphthofuran 2a, tert-butylamine and formaldehyde at toluene reflux led to the furonaphthoxazine 3e, which decomposes to afford an o-quinonemethide intermediate 5. The latter was trapped with 1-morpholinopropene to give a dihydro furonaphthopyran derivative 6. All compounds 2, 3, 4 and 6 were assayed for in vitro cytotoxic activity toward L 1210, MDA-MB 231 and PC tumor cells. Among them, furonaphth[1,3]oxazines 3b, 3c, and furo[1,3]oxazinoquinolines 4c, 4d showed significant activity against L 1210 cells, while furoquinoline 2b was the most cytotoxic compound towards all three cell lines.

Synthesis and in vitro cytotoxic activity of aza- and diazaanthraquinone derivatives.

Some 1,4-dihydro aza- and 1,4-dihydro diazaanthraquinone derivatives have been synthesized and submitted to in vitro cytotoxicity tests towards L 1210, MDA-MB 231 and PC3 cell lines. Some of the new substances showed significant activity.

Analysis of Usnea fasciata crude extracts with antineoplastic activity.

Different fractions, isolated from the lichen Usnea fasciata, were analyzed by PC, TLC, and RP-HPLC. Analysis of the organic phases, mainly containing phenolics, revealed that usnic acid is the main product from secondary metabolites, whereas the polysaccharides isolichenin and raffinose are the most abundant water-soluble carbohydrates. Fractions containing usnic acid, as well as those containing isolichenin, showed moderate activity against sarcoma 180 and Ehrlich tumor cells. High antitumoral activity, near 90% inhibition, was found associated with the fraction containing raffinose.

Determination of 8-methoxypsoralen kinetics: a relevant factor in the treatment of psoriasis by psoralen plus ultraviolet A therapy.

We compared the efficacy of psoralen plus ultraviolet A (UVA) therapy in 2 groups of psoriatic patients: a group of patients treated by a protocol adapted to the results of 8-methoxypsoralen (8-MOP) plasma kinetics (kinetics group) versus a control group of patients treated according to Pathak's standard protocol (UVA exposure 2 h after oral administration of a dose of 8-MOP equal to 0.6 mg/kg) (control group). The 8-MOP plasma kinetics were determined before the beginning of treatment. The parameter for comparison is the rapidity of clearing, taking into account the number of UVA exposures and UVA joules received. The analysis of the results observed show a 26.6% decrease in the number of UVA exposures and a 38.4% decrease in the dose of UVA received. These results are confirmed by the individual analysis of the rapidity with which the clearance of psoriatic lesions was obtained in patients who were treated with the standard PUVA protocol during the first attack and with the adapted protocol during the second attack.

[Influence of retinoids on the bioavailability of methoxy-8-psoralen]. / Influence des rétinoïdes sur la biodisponibilité du méthoxy-8-psoralène.

The retinoid-PUVA combination has been recognized as a satisfactory treatment of psoriasis. The absorption of 8-methoxypsoralen (8-MOP) is subject to wide interindividual variations under the influence of factors that are not yet known with certainty but are independent of age, sex and food taken at the same time as the psoralen. Whether concomitant retinoid administration influences the bioavailability of 8-MOP was considered an interesting question. The pharmacokinetics of 8-MOP were studied and compared in two populations of psoriatic patients: 119 patients treated with PUVA alone (psoralen-ultraviolet A) and 40 patients treated with the etretinate-PUVA combination (RePUVA). 8-MOP was assayed by the modified Ljunggren method 1 h, 1 h 30, 2 h, 2 h 30, 3 h and 4 h after ingestion of 8-MOP. The pharmacokinetic values recorded were: time and peak value of maximum plasma 8-MOP concentration (Tmax, Cmax) and area under the curve of time-related 8-MOP concentrations (AUC). The results obtained were as follows: Tmax PUVA 2 h 02 +/- 53 min RePUVA 1 h 56 +/- 50 min Cmax PUVA 159.12 +/- 88.85 ng/ml RePUVA 163.63 +/- 92.85 ng/ml AUC PUVA 343.33 +/- 211.06 ng*h/ml RePUVA 388.12 +/- 251.03 ng*h/ml Statistical analysis showed no significant difference in pharmacokinetic values between patients on PUVA alone and patients on RePUVA. Taking etretinate therefore does not alter the pharmacokinetics of 8-MOP and should not require any change in PUVA treatment.

In vitro and in vivo antitumoral activity of free, and encapsulated taxol.

The anti-tumoral activity of taxol encapsulated either in liposomes or in nanocapsules was compared with that of free taxol, using the P388 and L1210 leukaemia test systems. The in vitro inhibition of cell growth was measured after 48 h and 96 h exposure to various concentrations of taxol. With P388 cells, the inhibitory activities of the three forms of the drug were similar. With the L1210 cells, however, the concentrations required for a 50 per cent inhibition of cell growth (IC50) after 48 h exposure to the drug were greater for nanocapsules than for liposomes or free taxol, the values being 0.060, 0.043 and 0.035 micrograms ml-1, respectively. However, a greater efficiency of nanocapsules was observed after 96 h exposure. Using cytomorphometric analysis, no difference was found between L1210 cells treated either with free or encapsulated taxol. In vivo, mice bearing P388 leukaemia, and treated either with taxol solubilized with 5 per cent DMSO + 5 per cent cremophor in saline solution, or with taxol encapsulated in liposomes (IP daily dose of 12.5 mg Kg-1 body weight x 4 days) showed ILS values of 65.8% and 67.9% respectively. Nanocapsules proved to be toxic, apparently due to their composition: this problem is currently under investigation.

Antibacterial, antifungal and antitumoral activities of Micromycetes. I. Preliminary study.

The ability of 211 strains of Micromycetes to produce antibiotic, antifungal and antitumoral compounds has been investigated in vitro using test strains and P 388 leukemia cells. Cytotoxicity was determined on Vero cells. Convenient activities were obtained depending on the taxonomic group. Finally, 17 strains of Micromycetes were selected for their antibacterial or antifungal activities and 12 for their antitumoral properties. Investigations are in progress concerning these activities.

Influence of the diet on the plasma kinetics of 8-methoxypsoralen.

The plasma kinetics of 8-methoxypsoralen (8-MOP) have been determined in 103 patients treated by PUVA in the routine conditions in which PUVA therapy is carried out in hospital. 8-MOP is taken with breakfast; four types of breakfast were available, which differed by their lipid content; this study showed that the diet has no influence on the bioavailability of 8-MOP.