Photoswitching off the Antiproliferative Activity of Combretastatin A-4 Analogues.

The photostability and antiproliferative activity of combretastatin A-4 (CA-4) analogues against human epidermoid carcinoma cells A-431 were studied. For the first time, it was shown that UV or sunlight irradiation of furanone analogues of CA-4 results in a photorearrangement giving products with relatively low antiproliferative activity. The observed ability of this series CA-4 to the photodegradation can be used for the design of a new class of drug candidates with high selectivity to cancer cells.

Correlation between antioxidant activity of garlic extracts and WEHI-164 fibrosarcoma tumor growth in BALB/c mice.

The biological activities of garlic may be affected by different processing methods. This study, therefore, aimed to evaluate potential anticancer effects of different type of processed garlic extracts on WEHI-164 tumor cells in inbred BALB/c mice and correlate the tumor growth rates with some garlic constituents. In a preclinical trial 60 BALB/c mice were injected with WEHI-164 tumor cells and divided into six groups of 10 animals. Group 1 mice received 200 µL of saline, and groups 2-6 were injected intraperitoneally with fresh, microwaved, 3-month-old, leaves, and boiled garlic extracts, respectively, at 20 mg/kg/0.2 mL. Three weeks following tumor inoculation, the mean tumor size in garlic extract-treated groups was reduced with significant reductions observed in the fresh and microwaved extract groups compared with the control group (P<.05). The antioxidant capacity and the amounts of allicin, flavonoids, and phenolic compounds in differentially processed garlic were evaluated and correlated with their anticancer activities. There was a linear correlation between the amounts of allicin, flavonoids, or phenolic components derived from fresh, microwaved, 3-month-old, leaves, and boiled garlic and cancer growth prevention. In conclusion, garlic has anticancer activity against WEHI-164 tumor cells, and processing such as heating reduces its effect dramatically. The anticancer activities of different kinds of garlic are related to the level of allicin, flavonoids, and phenolic components. Therefore, fresh garlic has the highest content of bioactive components and the greatest anticancer efficacy.

In vitro photo-induced cytotoxic activity of Citrus bergamia and C. medica L. cv. Diamante peel essential oils and identified active coumarins.

CONTEXT: The search for innovative therapeutic approaches is gaining more interest in clinical oncology. OBJECTIVE: In the present investigation we reported the chemical profile and the photo-induced cytotoxic activity of two endemic Calabrian Citrus species (Rutaceae): Citrus bergamia Risso & Poit. and Citrus medica L. cv. Diamante. MATERIALS AND METHODS: Essential oils were obtained by hydrodistillation and analyzed by GC and GC/MS. In order to evaluate the cytotoxic activity two melanoma models, such as amelanotic melanoma C32 and malignant melanoma A375, were used. RESULTS: The essential oil of C. bergamia was characterized by limonene, linalyl acetate, gamma-terpinene, linalool and beta-pinene as major components. The most abundant compounds of C. medica cv. Diamante oil were limonene, gamma-terpinene, citral, geranial, beta-pinene and alpha-pinene. Two coumarins, bergapten and citropten, were also identified in C. bergamia and C. medica cv. Diamante, respectively and tested for biological activity. Both C. bergamia and C. medica cv. Diamante oils exhibited a selective interesting activity against the A375 cell line with IC(50) values of 79.3 and 89.1 microg/mL, respectively, after 100 min exposure to UV irradiation. The strong antiproliferative activity demonstrated with bergapten (IC(50) value of 71.3 microg/mL after 20 min of irradiation) was not found with citropten. DISCUSSION AND CONCLUSION: Our study suggested that UV irradiation is effective in activating essential oils and in particular bergapten. This phototoxicity may be considered as a treatment option in some cases of lentigo maligna or lentigo maligna melanoma.

Stability of docetaxel diluted to 0.3 or 0.9 mg/mL with 0.9% sodium chloride injection and stored in polyolefin or glass containers.

PURPOSE: The stability of docetaxel diluted to 0.3 or 0.9 mg/mL with 0.9% sodium chloride injection and stored in polyolefin or glass containers was studied. METHODS: Vials of docetaxel injection concentrate were reconstituted with the entire contents of the solvent vial and carefully homogenized to avoid the formation of foam. Solutions were aseptically prepared with nominal docetaxel concentrations of 0.3 and 0.9 mg/mL by adding the appropriate quantities to polyolefin containers or glass bottles, to which had been added the appropriate volume of 0.9% sodium chloride injection, yielding a final volume of 50 mL. Three identical polyolefin containers and one control glass bottle for each concentration were prepared. All test solutions were stored at 19-21 degrees C and protected from light. Chemical stability was measured by using a stability-indicating high-performance liquid chromatographic (HPLC) assay with ultraviolet-light detection. Physical stability was determined by visual inspection. RESULTS: No evidence of precipitation was observed during the first 24 hours of the study. However, after a day of storage, the HPLC assay revealed large relative standard deviation values for diluted docetaxel solutions in some containers. These values were predictive for the formation of precipitates and compatible with the existence of microprecipitates at 24 hours. These results suggest that the diluted docetaxel infusions were not stable when stored at 19-21 degrees C. CONCLUSION: Docetaxel 0.3 and 0.9 mg/mL in 0.9% sodium chloride injection was not physically stable for more than one day when stored at 19-21 degrees C. Docetaxel stability in diluted solutions appears sensitive to slight changes in temperature and degree of agitation.

The influence of ultraviolet radiation on the content of pharmacologically active taxoids in yew tissues.

The aim of the work was the investigation of the influence of UV radiation on the taxoids contents in yew tissues. The experiment was performed using Taxus baccata var. Aurea Corr. twigs irradiated with UV C (lambda = 254 nm) and UV A (lambda = 366 nm) in comparison to control samples. Multistep procedure of sample preparation was applied before the analysis of paclitaxel and 10-DAB III: SPE using alumina - for purification from the chlorophylles, waxes and polar balasts as well as zonal micropreparative TLC on silica - for isolation of partially separated fractions. The quantitation of some taxoids in the isolated fractions was performed using RP-HPLC procedure in system C18/acetonitrile + water. The experiments with UV-A and especially UV-C radiation showed changes in concentrations of paclitaxel and its precursor-10-deacetylbaccatin III. The results can be utilized to increase the yield of the taxoids isolated for medicinal and practical purposes.

Allixin induction and accumulation by light irradiation.

Allixin, a phytoalexin isolated from garlic, was induced by irradiating fresh garlic cloves with sunlight or UV light. Induced allixin was analyzed by HPLC, and the accumulated amounts of allixin were 3.1-6.3 microg/g under experimental conditions.

Alkaloid-fullerene systems through photocycloaddition reactions.

The photocycloaddition of tertiary amines to ¿60fullerene (C(60)) is an interesting and useful reaction. We wished to extend the applications of this type of reaction through an investigation of the photoaddition of alkaloids to C(60) for the purpose of synthesizing novel and complex photoadducts that are difficult to obtain by usual methods. Irradiation of tazettine (2) or gramine (3) with C(60) in toluene leads to formation of one monoadduct (6 or 7), whereas scandine (1a) or 10-hydroxyscandine (1b) reacts with C(60) photochemically to give two products, the expected ¿6,6 monoadduct (5a, 5b) and a new type of monoadduct with a bis-¿6, 6 closed structure (4a, 4b). These new structures were characterized by UV-vis, FT-IR, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, ROESY, HMQC (heteronuclear multiple-quantum coherence), and HMBC (heteronuclear multiple-bond connectivity) spectroscopy. The techniques of time-of-flight secondary ion MS (TOF-SIMS) and field desorption MS (FD-MS) were used for the mass determination. (3)He NMR analysis of the product mixture from photoaddition of 1a to C(60) containing a (3)He atom ((3)He@C(60)) led to two peaks at -9.091 and -11.090 ppm relative to gaseous (3)He, consistent with formation of a ¿6, 6-closed monoadduct and a bis-¿6,6 closed adduct. Presumably, the bis-¿6, 6 closed adducts are formed by an intramolecular ¿2 + 2 cycloaddition of the vinyl group to the adjacent 6,6-ring junction of C(60) after the initial photocycloaddition.

Syntheses of taxuspine C derivatives as functional inhibitors of P-glycoprotein, an ATP-associated cell-membrane transporter.

UV-Irradiation of taxinine and related compounds in acetonitrile induced a smooth transannulation between the C-3 and C-11 positions without any influence from the C-2, C-9 and C-10 substituents to give tetracyclic taxuspine C derivatives in almost quantitative yields. Photochemical transannular reaction of taxoids possessing a cinnamoyl group in the side-chain was accompanied by an E,Z-isomerization of the cinnamoyl moiety. Cellular accumulation of vincristine, a useful drug for cancer chemotherapy, in multidrug-resistant ovarian cancer cells was found to increase most effectively in the case of 5-O-benzoylated 5-O-decinnamoyltaxuspine C. This indicates that the 5-O-benzoylated taxuspine C derivative may be a promising functional inhibitor of P-glycoprotein, which acts as an ATP-associated efflux pump for cancer chemotherapeutic agents.

In vitro evaluation of Taxol combined with radiations in human squamous cell carcinoma spheroids.

The effect of Taxol on the radiation sensitivity of human squamous carcinoma of the head and neck region was determined in vitro, using clonogenic assays and multicellular tumor spheroids (MTS). Radiosensitivity parameters were determined by alpha and beta for clonogenic assays, and by the residual/control volume ratios at 2 Gy (RSV2) and the dose inducing 50% decrease in MTS number (SCD50) for spheroids. In HTB43 and CAL27 colonies, the combination was antagonist. In spheroids, Taxol induced a decrease of RSV2 and SCD50 in HTB43 and CAL27 MTS and their combinations with radiation were synergistic and additive, respectively. Therefore, the different results obtained by clonogenic assays and MTS may suggest higher drug incorporation through the multiple cell layers of the spheroids than in monolayers.