lignans and Leukemia-P388

Bioassay (P388 lymphocytic leukemia cell line and human tumor cell lines)-guided separation of the extracts prepared from the tropical and coastal trees Hernandia peltata (Malaysia) and Hernandianymphaeifolia (Republic of Maldives) led to the isolation of a new lignan designated as hernanol (1) and 12 previously known lignans: (-)-deoxypodophyllotoxin (2), deoxypicropodophyllin (3), (+)-epiaschantin (4), (+)-epieudesmin (5), praderin (6), 5'-methoxyyatein (7), podorhizol (8), deoxypodorhizone (9), bursehernin (10), kusunokinol (11), clusin (12), and (-)-maculatin (13). The oxidative cyclization (with VOF(3)) of lignans 8, 9, and 10 resulted in a new and unusual benzopyran (14), isostegane (15), and a new dibenzocyclooctadiene lactone (16), respectively. The structure and relative stereochemistry of hernanol (1) and lignans 3, 7, 8, 9, 10, 11, and 12 were determined by 1D and 2DNMR and HRMS analyses. The structures and absolute stereochemistry of structures 2, 4, 5, 6, 13, 14, 15, and 16 were unequivocally determined by single-crystal X-ray diffraction analyses. Evaluation against the murine P388 lymphocytic leukemia cell line and human tumor cell lines showed podophyllotoxin derivatives 2 and 3 to be strong cancer cell line growth inhibitors and substances 4, 5, 8, and 15 to have marginal cancer cell line inhibitory activities. Seven of the lignans and one of the synthetic modifications (14) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.

Topics: Animals; Antineoplastic Agents, Phytogenic; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Indian Ocean Islands; Leukemia P388; Lignans; Malaysia; Mice; Microbial Sensitivity Tests; Molecular Conformation; Molecular Structure; Neisseria gonorrhoeae; Plants, Medicinal; Trees; Tumor Cells, Cultured

Four additional neolignans, comprising obovatifol [(2S,3S)-2,3-dihydro-2- (3,4-dihydroxy-5-methoxyphenyl)-7-methoxy-3-methyl-5-trans-propenyl benzofuran], obovaten [2-(3,4-dihydroxy-5-methoxyphenyl)-7-methoxy-3- methyl-5-trans-propenyl benzofuran], perseal C [(2S,3R)-2,3-dihydro-2-(3,4-methylenedioxyphenyl)-5- formyl-3-hydroxymethyl-7-methoxy benzofuran] and perseal D [2-(3,4-dihydroxy-5-methoxyphenyl)-5-formyl-7- methoxy-3-methyl benzofuran] were isolated in a continuing study of the leaves of Persea obovatifolia. Obovatifol had been reported previously in a mass spectrometric analysis without any other spectroscopic data. Obovaten and perseals C and D are new compounds, bearing a C-1' formyl side-chain, instead of a propenyl group. Their structures were elucidated from spectroscopic data; they showed significant cytotoxic activities against P-388, KB16, A549 and HT-29 cancer cell lines in vitro.

Topics: Animals; Cell Survival; Cytotoxins; Humans; KB Cells; Leukemia P388; Lignans; Mice; Molecular Structure; Plant Extracts; Plant Leaves; Tumor Cells, Cultured

A series of fused pyrazole derivatives of cyclolignans have been prepared through simple chemical routes and evaluated for their cytotoxic activities in culture cells of P-388 murine leukemia, A-549 lung carcinoma and HT-29 colon carcinoma. Despite the lack of the lactone moiety in their structures, they show IC50 values at microM levels.

Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; HT29 Cells; Humans; Leukemia P388; Lignans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Mice; Pyrazoles; Structure-Activity Relationship

By means of activity-directed chromatographic fractionation using cultured astrocytoma (ASK) cells, six dibenzocyclo-octadiene lignans were isolated from Steganotaenia araliacea stem bark. In addition to the most abundant analogue, steganangin [1], two other known compounds, steganacin [3] and steganolide A [6], and three new compounds, episteganangin [2], steganoate A [4], and steganoate B [5], were obtained. Episteganangin [2] was chemically correlated with the known ketone steganone [7]. All of these compounds demonstrated cytotoxic activity when tested against a panel of eleven human tumor cell lines, with the exception of steganoate A [4]. The magnitude of this activity tended to correlate with antimitotic activity observed with the ASK assay and in vitro inhibition of microtubule assembly. Steganacin [3] was less cytotoxic than colchicine, but more active in these latter two assay systems.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Survival; Drug Screening Assays, Antitumor; Humans; Leukemia P388; Lignans; Mice; Microtubules; Plants, Medicinal; Tubulin; Tumor Cells, Cultured

Complete 1H-nmr data and unambiguous assignments of the 13C-nmr spectra of phyllanthin [1] and hypophyllanthin [2] were obtained through extensive nmr studies, including homonuclear COSY, homonuclear decoupling, APT, HETCOR, nOe difference, selective INEPT, and COLOC experiments. The absolute configuration of hypophyllanthin [2] was determined by cd. Neither of these lignans demonstrated significant cytotoxic activity when evaluated with a battery of cultured mammalian cells, but both were found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB cells. In addition, 1 was found to displace the binding of vinblastine with membrane vesicles derived from this cell line, suggesting an interaction with the P-glycoprotein.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Membrane; Cell Survival; Drug Resistance; Drug Synergism; Glycoproteins; Humans; KB Cells; Leukemia P388; Lignans; Lignin; Magnetic Resonance Spectroscopy; Tumor Cells, Cultured; Vinblastine

Nine lignan derivatives (4-12) have been obtained from (-)-yatein by treatment with DDQ and NBS. They showed moderate antineoplastic activity (P-388, A-549, HT-29) compared with podophyllotoxin, but some of them have a better therapeutic index. None of the tested compounds shows anti-viral (HSV-1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activities.

Topics: Adenosine Deaminase Inhibitors; Animals; Antineoplastic Agents; Antiviral Agents; Enzyme Inhibitors; Folic Acid Antagonists; Glutathione Transferase; Humans; Leukemia P388; Lignans; Lignin; Mice; Mice, Inbred DBA; Neoplasms, Experimental

Topics: Animals; Cardiovascular Agents; Cyclooctanes; Doxorubicin; Drugs, Chinese Herbal; Free Radical Scavengers; Leukemia P388; Lignans; Malondialdehyde; Mitochondria, Heart; Phenanthrenes; Polycyclic Compounds

Topics: Animals; Antineoplastic Agents, Phytogenic; Furans; Leukemia P388; Lignans; Mice; Plants

Two antileukemic daphnane esters, Pimelea factor P2 (I) and the new compound dircin (II), were isolated from the twigs and flowers of Dirca occidentalis A. Gray (Thymelaeaceae). Three lignans, (-)-medioresinol (III), (+)-syringaresinol (IV), and (-)-lariciresinol (V), as well as the coumarin daphnoretin (VI), were found to be additional cytotoxic constitents of this taxon.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Survival; In Vitro Techniques; Leukemia P388; Lignans; Mice; Plant Extracts