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.

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.

Antitumoral activity of patulin and patulin-cysteine adducts.

A comparison between the cytotoxicity and the anti-tumoral activity of patulin and patulin-cysteine adducts has been conducted. In vitro assays using L 1210 and P 388 cells showed that patulin-cysteine adducts had less cytotoxic activity than patulin (IC50 was 4 fold of IC50 patulin). In vivo, cysteine not only reduced the toxicity of patulin but also reduced its antitumoral activity against L 1210 and P 388 mouse leukemias (respectively of 25.7% and 46.6% with 3 mg.kg-1.d-1). By addition on patulin at the 4 or 7 position, cysteine might interfere with the lactone function and the -CH2- in in position 6 which are responsible for the antitumoral activity.

Antimicrobial and antitumoral activities of 6-allyl-5,6-dihydro-5-hydroxypyran-2-one, a lactone produced by a new Drechslera species.

Antifungal, antibacterial and antitumoral properties of 6-allyl-5,6-dihydro-5-hydroxypyran-2-one were researched. This compound was isolated from culture medium of a new Drechslera species from the area of the Dead Sea. The product exhibited a large activity spectrum against microorganisms, with interesting IC 50 values close to those obtained with reference compounds (kanamycin and ketoconazole). Antitumoral potentiality was 10 to 58 times less important than with doxorubicin, however IC 50 obtained were below 4 micrograms/ml, which is the threshold value proposed by National Cancer Institute for preliminary screening of active molecules.

[Annomonysvin: a new cytotoxic gamma-lactone-monotetrahydrofuranyl acetogenin from Annona montana]. / Annomontacine: une nouvelle acétogénine gamma-lactone-monotetrahydrofurannique cytotoxique de l'Annona montana.

The structure of annomontacin [I], a novel monotetrayhydrofuran fatty acid gamma-lactone (acetogenin) isolated from the seeds of Amnona montana, was determined by spectral analysis. The cytotoxicities in vitro of annomontacin [I], annonacinone [2], and annonacin were measured against murine leukemia L1210, human breast adenocarcinoma MDA-MB231, and human breast carcinoma MCF7 cell lines and compared with adriamycin.

Synthesis of Mannich bases of 5-hydroxynapthalene-1,8-carbolactone as potential antifungal or antitumor agents.

Mannich bases of 5-hydroxynaphthalene-1,8-carbolactone 1 were prepared from various secondary amines or bulky primary amines and formaldehyde. They were isolated in almost all cases as hydrochlorides. These derivatives were submitted to in vitro antifungal and cytotoxic assays. The antifungal assays were performed against three strains of yeasts and five strains of human pathogenic fungi. Two of the tested compounds, 2i and 2j, exhibited interesting antifungal activities against Candida albicans and Candida tropicalis. The cytotoxic activity was evaluated towards L 1210 leukemia cells. Almost all of the Mannich bases had shown significant activity against this tumor cell line as values of IC50 less than or equal to 4 micrograms/ml are considered interesting. Only one derivative 2 developed better cytotoxicity than the parent compound 1.

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.

[Tamoxifen fluorescence as a marker of hormone-dependence: physicochemical aspects]. / La fluorescence du tamoxifène comme marqueur de l'hormonodépendance: aspect physico-chimique.

In acid solutions, Tamoxifen is protonized and forms with eosin a fluorescent ionic association (lambda exc 480 nm, lambda em 565 nm). This reaction is quantitatively linked to the concentration of Tamoxifen. Thus the Tamoxifen induced fluorescence observed in hormone-dependent malignant breast tumor cells after Papanicolaou staining procedure, appears as a consequence of the binding of Tamoxifen to eosin.