chiniofon and Leukemia-P388

Selective acylation of the phenolic hydroxyl group of 10-hydroxycamptothecin has been accomplished using phenyl dichlorophosphate. Additional modification of the 10-OH as an ether permits a 20-acyl derivative to be synthesized. This result along with data from a 6-hydroxyquinoline model strongly suggests that powerful intermolecular hydrogen bonding exists in the parent molecule.

Topics: Acylation; Animals; Antineoplastic Agents; Camptothecin; Carboxylic Acids; Hydrogen Bonding; Hydroxyquinolines; Indicators and Reagents; Leukemia P388; Magnetic Resonance Spectroscopy; Neoplasms; Polyethylene Glycols; Rats; Tumor Cells, Cultured

Bioassay (P388 lymphocytic leukemia cell line and human cancer cell lines)-guided separation of an extract prepared from the stem bark and twigs of the previously uninvestigated Ruprechtia tangarana led to the isolation of a new isocarbostyril designated ruprechstyril (1), secalonic acid A (2), 2'-O-methylevernic acid (3), 3,3',4-tri-O-methylflavellagic acid (4), lichexanthone (5), methyl asterrate (6), and 3beta,22E,24S-stigmasta-5,22-dien-3-ol (7). Only secalonic acid A exhibited cancer cell and microbial growth inhibition. The structure of ruprechstyril (1) was determined by HRMS and 1D and 2D NMR spectra and confirmed by single-crystal X-ray analysis. The structures and absolute stereochemistry of five of the other compounds were also established by X-ray crystal structure determination.

Topics: Animals; Antineoplastic Agents, Phytogenic; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Hydroxyquinolines; Leukemia P388; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Peru; Plants, Medicinal; Polygonaceae; Stereoisomerism

Novel indolo[3,2-b]quinoline derivatives (1c--f), which carried a methoxy or a hydroxy group at the 4- or 7-position of the lead compound 1a, were prepared and their antitumor activities against P388 in mice were examined. Except for the 4-hydroxy derivative (1d), these showed remarkably potent activity. Among these compounds, the 7-hydroxy derivative (1f) was the most potent one (optimal dose = 50 mg/kg, the median survival time of treated group/control group (T/C) greater than 330%, cure = 5/6).

Topics: Animals; Antineoplastic Agents; Hydroxyquinolines; Indoles; Leukemia P388; Magnetic Resonance Spectroscopy; Mice

The bis derivative 6 of 8-hydroxyquinoline, which, like tropolones, readily forms a chelate, was synthesized and found to have high potency (dose = 12.5 mg/kg, T/C % = 164) against leukemia P388 in mice approximately equivalent to that of the bistropolone 1b. 8-Hydroxyquinoline analogues with broad structural variation were synthesized and their structure-activity relationships followed the same pattern as in the tropolone series. In addition, the bistropolones 1a-e were tested for their ability to bind to tubulin and found to have no such property. The results of this study suggested that bistropolone and bis(8-hydroxyquinoline) derivatives must form a chelate with the metal necessary for the enzyme, such as ribonucleotide reductase, which catalyzes the DNA biosynthetic pathways.

Topics: Animals; Antineoplastic Agents; Colchicine; Cycloheptanes; Hydroxyquinolines; Leukemia P388; Mice; Oxyquinoline; Structure-Activity Relationship; Tropolone

Topics: Animals; Antibiotics, Antineoplastic; Drug Evaluation, Preclinical; Hydroxyquinolines; Leukemia L1210; Leukemia P388; Leukemia, Experimental; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Quinolines