nsc-600032 and Neoplasms

A rat model was developed to enable direct administration of hyperpolarized. Rat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized. Intra-arterial infusion of hyperpolarized. The model maximizes tumor substrate/drug delivery and minimizes T

Topics: Animals; Arteries; Carbon Isotopes; Drug Delivery Systems; Epigastric Arteries; Female; Femoral Vein; Gadolinium; Magnetic Resonance Spectroscopy; Male; Neoplasm Metastasis; Neoplasms; Optical Imaging; Perfusion; Phosphorylation; Pyruvic Acid; Rats; Spectrophotometry; Stilbenes

Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI 50 = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC 50 = 2.8 microM). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.

Topics: Animals; Antineoplastic Agents; Bibenzyls; Disease Models, Animal; Drug Design; Drug Screening Assays, Antitumor; Humans; Inhibitory Concentration 50; Leukemia P388; Mice; Molecular Structure; Neoplasms; Regional Blood Flow; Stilbenes; Tubulin

A novel series of dihydronaphthalene and benzosuberene analogs bearing structural similarity to the combretastatins in terms of 1,2-diarylethene, trimethoxyphenyl, and biaryl functionality has been synthesized. The compounds have been evaluated in regard to their ability to inhibit tubulin assembly and for their cytotoxicity against selected human cancer cell lines. From this series of compounds, benzosuberene analogs 2 and 4 inhibited tubulin assembly at concentrations comparable to that of combretastatin A-4 (CA4) and combretastatin A-1 (CA1). Furthermore, analog 4 demonstrated remarkable cytotoxicity against the three human cancer cell lines evaluated (for example GI(50)=0.0000032 microM against DU-145 prostate carcinoma).

Topics: Antineoplastic Agents; Benzocycloheptenes; Bibenzyls; Cell Line, Tumor; Cell Proliferation; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Models, Molecular; Molecular Structure; Naphthalenes; Neoplasms; Stereoisomerism; Structure-Activity Relationship; Tubulin