naphthoquinones and Leukemia-P388

A series of nine new compounds bridged by acyl groups at the 5,8-dihydroxyl group of DHNQ were synthesized and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor action in mice bearing S-180 cells in the peritoneal cavity was also assessed. Increasing the size of the acyl group (compounds 7-9) up to propyl increased the antitumor activity (T/C value), whereas the cytotoxicity of these compounds was comparable against L1210 (lymphocytic leukemia) and P388 (lymphoid neoplasm) cancer cells. Further increasing in the chain length (compounds 11-15) decreased the potency. Thus, acyl group chains of three carbon atoms is optimal for antitumor activity. The most potent compound of this series was 2-[N-methyl-N-(4-methyl-1,3-benzothiazol-2-yl)aminomethyl]-5,8-dipropylcarbonyloxy-1,4-naphthoquinone (compound 9) with a T/C (%) value of 354.

Topics: Animals; Antineoplastic Agents; Drug Screening Assays, Antitumor; Leukemia L1210; Leukemia P388; Male; Mice; Mice, Inbred ICR; Naphthoquinones; Neoplasm Transplantation; Sarcoma 180; Structure-Activity Relationship; Tetrazolium Salts; Thiazoles

Three new compounds designated as firmianones A, B, and C (1-3), along with 13 known compounds, were isolated from the roots of Firmiana platanifolia. Their structures were elucidated by interpretation of HRESIMS, 1H-1H COSY, HMQC, HMBC, and NOESY. The absolute configurations of firmianones A and B with a rare hexacyclic skeleton were determined by CD exciton-coupling experiments. Firmianones A and B exhibited moderate cytotoxicity to the P388 cancer cell line.

Topics: Animals; Circular Dichroism; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Leukemia P388; Malvaceae; Mice; Molecular Structure; Naphthoquinones; Plants, Medicinal; Tumor Cells, Cultured

The hollow fiber test has been developed for the preliminary in vivo assessment of cancer chemotherapeutic efficacy of selected natural products. Using this model, we have established growth conditions for HL-60, HUVEC, Ishikawa, KB, KB-V1, LNCaP, Lu1, MCF-7, Mel2, P-388, and SW626 cells implanted at the intraperitoneal (i.p.) and subcutaneous (s.c.) compartments of athymic mice. Five cytotoxic natural product isolates (2-6) were tested in this model, along with paclitaxel (taxol) (1). Among the compounds tested, dioscin (2) and 13-methoxy-15-oxozoapatlin (3) were found to be active, indicating their potential to function as cancer chemotherapeutic agents. On the other hand, ochraceolide A (4), alpha-lapachone (5), and 2-(1-hydroxyethyl)naphtha[2,3-b]furan-4,9-quinone (6), all of which were significantly cytotoxic to cultured mammalian cells, did not mediate significant responses with the hollow fiber model. In further xenograft studies using KB cells implanted at the subcutaneous site, compound 3 mediated a statistically significant response which was consistent with the response observed at the subcutaneous compartment in the hollow fiber tests. In sum, these studies illustrate the usefulness of the hollow fiber model in natural product drug discovery programs. Preliminary indications of potential therapeutic efficacy can be provided quickly at relatively low expense. Agents capable of mediating a response at the subcutaneous site would appear to warrant greatest attention.

Topics: Animals; Biological Factors; Colonic Neoplasms; Diosgenin; Disease Models, Animal; Diterpenes; Drug Screening Assays, Antitumor; Female; Heterocyclic Compounds, 3-Ring; HL-60 Cells; Humans; Inhibitory Concentration 50; KB Cells; Leukemia P388; Male; Melanoma; Mice; Molecular Structure; Naphthoquinones; Ovarian Neoplasms; Paclitaxel; Polymers; Prostatic Neoplasms; Triterpenes; Tumor Cells, Cultured

A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo.

Topics: Animals; Antibiotics, Antineoplastic; Culture Media; Drug Screening Assays, Antitumor; Fermentation; Humans; Indoles; Leukemia P388; Magnetic Resonance Spectroscopy; Mice; Naphthoquinones; Spectrophotometry, Ultraviolet; Streptomyces; Tumor Cells, Cultured

Cycloalkanin was accessible by a practical and efficient asymmetric synthesis. The chiral center of the target is introduced via an asymmetric C-arylation of chiral aldehyde in high de. The synthesized cycloalkanin was shown to be significantly active against P388 cell line as assayed by in vitro MIT method.

Topics: Animals; Antineoplastic Agents; Drug Screening Assays, Antitumor; Leukemia P388; Molecular Structure; Naphthoquinones

Coordinately unsaturated Cu(II) and Fe(III) complexes of the stoichiometry [Cu(L)Cl] and [Fe(L)Cl2], where L = tridentate anion of 2-hydroxy-1,4-naphthoquinone 1-thiosemicarbazone (2HNQTSC) and its 3-methyl derivative (3M2HNQTSC), were screened in vitro against P388 lymphocytic leukemia cells. Copper complexes were found to be more effective inhibitors of DNA synthesis than analogous Fe(III) compounds. The inhibitory activities are suggested to be related to Cu(II)-Cu(I) redox couple or nitrogen adduct formation.

Topics: Animals; Antineoplastic Agents; Chelating Agents; Copper; DNA; Iron Chelating Agents; Leukemia P388; Lymphocytes; Mice; Naphthoquinones; Thiosemicarbazones

A new diterpenoid quinone, named sapriparaquinone (1) was isolated from the root of Salvia prionitis Hance. 1 was identified as 3-hydroxy-6-methyl-2-(1-methyl)-5-(4-methylpenten-3-yl)-1, 4-naphthoquinone by spectral analysis and chemical transformation of saprorthquinone (2). 1 and 2 are 4,5-seco-5, 10-frideoabietane derivatives and must be biogenetically derived from an abietane structure. Like 2, 1 also showed cytotoxicity against P388 leukemia cells.

Topics: Animals; Chemical Phenomena; Chemistry; Diterpenes; Drugs, Chinese Herbal; Leukemia P388; Mice; Naphthoquinones; Tumor Cells, Cultured

By reacting three quinolizidinylalkylamines with 1,4-naphtoquinone, 2,3-dichloronaphto-1,4-quinone and 1-chloroanthraquinone nine compounds were obtained which are of interest as antitumoral, antiviral, antibacterial and antiparasitic agents. These compounds, so far, have been tested against lymphocytic leukemia P 388 in mice and found inactive.

Topics: Animals; Anthraquinones; Antineoplastic Agents; Chemical Phenomena; Chemistry; Leukemia P388; Leukemia, Experimental; Mice; Mice, Inbred Strains; Naphthoquinones; Quinolizines