Diterpenoid Alkaloids from Aconitum tanguticum

A new 19,21‐secohetisan diterpenoid alkaloid, tangutisine B ( 1 ), was isolated from the aerial parts of Aconitum tanguticum (Maxim. ) Stapf. , together with pacidine, 14‐deacetylajadine. The structure of 1 was determined by an interpretation of 1D‐ and 2D‐NMR together with X‐ray crystallographic data. Bioactivities of the isolates were tested in the P‐388, Bel‐7402, Cox‐2, and caspase‐3 assays.     

Studies on thermophile products. IV. Structural elucidation of cytotoxic substance, BS-1, derived from Bacillus stearothermophilus.

A new cytotoxic substance designated as BS-1 was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563. On the basis of spectral data, the structure of BS-1 was determined as bis(2-hydroxyethyl) trisulfide and confirmed by direct comparison with the synthetic compound. BS-1 exhibited potent cytotoxicity against leukemia P388-D1, leukemia P388, mastocytoma P815, lymphoma EL4 and lymphoma MOLT4.     

New Eunicellin Diterpenes and 9,10‐Secosteroids from the Gorgonian Muricella sibogae

Bioactivity‐guided isolation of the rare gorgonian Muricella sibogae (Nutting ) yielded the two new eunicellin diterpenes sibogin A and B ( 1 and 2 ), the three new 9,10‐secosteroids sibogol A–C ( 6 – 8 ), together with the three known eunicellin diterpenes 3 – 5 and the five known 9,10‐secosteroids 9 – 13 . Their structures were established by extensive spectral analysis (1D‐ and 2D‐NMR, IR, and MS). The cytotoxicity of the isolates 1 – 13 was evaluated in vitro against the selected tumor cell lines P388 and BEL‐7402. All the compounds showed only weak activity against P388 cell lines, with an inhibition rate ranging from 10 to 60% at a concentration of 50 μg/ml, whereas the were inactive against BEL‐7402 cell lines.     

Cephalimysin A, a potent cytotoxic metabolite from an Aspergillus species separated from a marine fish

Cephalimysin A (1) was isolated from a strain of Aspergillus fumigatus originally separated from the marine fish Mugil cephalus, and its absolute stereostructure was elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations including the modified Mosher’s method. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.     

Additional cytotoxic substances isolated from the sponge-derived Gymnascella dankaliensis

A continuous investigation of secondary metabolites produced by the sponge-derived fungus, Gymnascella dankaliensis, has yielded a new polyketide tyrosine derivative, dankastatin C (3) and the known steroid, demethylincisterol A₃ (4), which was originally found from a Homaxinella marine sponge. The stereostructure of the new compound has been determined based on the analysis of 1D and 2D NMR data. Dankastatin C (3) showed potent cell growth inhibitory activity against the murine P388 cell line.     

Absolute stereostructures of cytotoxic metabolites, chaetomugilins A-C, produced by a Chaetomium species separated from a marine fish

Chaetomugilins A-C were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques, some chemical transformations, and an X-ray analysis. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.     

Synthesis and evaluation of novel N-substituted-6-methoxynaphthalene-2-carboxamides as potential chemosensitizing agents for cancer

A novel class of molecules with structure N-[3-(heteroaryl)propyl]-6-methoxynaphthalene-2-carboxamides 8-13 were synthesized by condensing 6-methoxy-2-naphthoyl chloride 1 with 3-(heteroaryl)propyl amines 2-7. Compounds 8-12 were evaluated in vitro, in P388 murine lymphocytic leukemia cell line (P388) using SRB assay for cytotoxicity and in adriamycin resistant P388 murine lymphocytic leukemia cell line (P388/ADR) using MTT assay for resistant reversal activity. Compounds 8-12 were non-toxic at lower dose of 20 microg/ml, and effectively reversed adriamycin resistance. However, at higher doses (40, 80 microg/ml) they showed significant cytotxicity and hence reversal potency was not determined at these concentrations.     

Agariblazeispirols A and B, an unprecedented skeleton from the cultured mycelia of the fungus, Agaricus blazei

Agariblazeispirols A and B, which have a unique steroidal skeleton, have been isolated from the cultured mycelia of Agaricus blazei (Agaricaceae). The absolute structure of Agariblazeispirol A was established to be (20S,22R,23R,24S)-13β,22:22,25-diepoxy-5-methoxy-14β-methyl-18-nor-des-A-ergosta-5,7,9,11-tetraen-23-ol by extensive 1D and 2D NMR spectral data, and X-ray analysis. The structure of Agariblazeispirol B was elucidated to be a stereoisomer of agariblazeispirol A at its carbon 22, (20S,22S,23R,24S)-13β,22:22,25-diepoxy-5-methoxy-14β-methyl-18-nor-des-A-ergosta-5,7,9,11-tetraen-23-ol by comparison of extensive 1D and 2D NMR spectral data with those of agariblazeispirol A. Both compounds showed a moderate circumvention of drug resistance on mouse leukemia P388/VCR cells.     

PORPHYRIN PHOTOSENSITIZATION OF MULTI-DRUG RESISTANT CELL TYPES

The P388 murine leukemia and P388/ADR, a subline expressing the multi-drug resistance (MDR) phenotype, were examined with regard to the role of MDR as a determinant of responsiveness to photodynamic therapy in vitro. Mesoporphyrin was used as a model substrate. We found no differences in porphyrin accumulation nor transport alterations associated with exposure of P388/ADR cells to the verapamil analog DMDP. There was a significant correlation between photodamage to mitochondria vs loss of cell viability in both cell lines, and LD50 sensitizer levels were not significantly different in P388 vs P388/ADR. P388/ADR cells were partly resistant to porphyrin-catalyzed photodamage to amino acid transport, but this result was not associated with differences in sensitizer localization, as indicated by fluorescence studies. Moreover, photodamage to membrane transport was not associated with loss of viability. These studies suggest that cells which express the MDR phenotype are unlikely to be cross-resistant to photodynamic therapy.     

Measurement of Prostaglandins from Biological Samples in the Subnanogram Range by Fluorescence Labelling and HPLC Separation

Abstract

Small amounts of different prostaglandins can be detected in the subnanogram range after derivatisation with the reactive fluorescence dye 9 - anthroyldiazo - methane (ADAM), followed by specific purification and HPLC separation. This method allows the measurement of PGE2 from supernatants of the murine macrophage - like cell line P388 D1 with quantitative recovery.     

Sesquiterpene Lactones from Daucus glaber

Six new sesquiterpene lactone esters, daucoguaianolactones A–F ( 1 – 6 ), and one new sesquiterpene lactone, daucoeudesmanolactone A ( 7 ) were isolated from the leaves and stems of Daucus glaber (Forssk .) Thell ., along with the known sesquiterpene lactones talasins A and B and badkhysin. The structures of 1 – 6 were established on the basis of extensive 1D‐ and 2D‐NMR spectroscopic studies and that of 7 by X‐ray crystallography. Compounds 4, 7 , and talasins A and B showed moderate cytotoxicity against P‐388 leukemia cells.     

Chaetomugilins I-O, new potent cytotoxic metabolites from a marine-fish-derived Chaetomium species. Stereochemistry and biological activities

Chaetomugilins I-O were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, as well as chemical transformations. These compounds exhibited significant growth inhibition of cultured P388, HL-60, L1210, and KB cell lines. In addition, chaetomugilin I showed selective cytotoxic activity against 39 human cancer cell lines.     

Biological activity of carbazole alkaloids and essential oil of Murraya koenigii against antibiotic resistant microbes and cancer cell lines

A total of three carbazole alkaloids and essential oil from the leaves of Murraya koenigii (Rutaceae) were obtained and examined for their effects on the growth of five antibiotic resistant pathogenic bacteria and three tumor cell lines (MCF-7, P 388 and Hela). The structures of these carbazoles were elucidated based on spectroscopy data and compared with literature data, hence, were identified as mahanine (1), mahanimbicine (2) and mahanimbine (3). The chemical constituents of the essential oil were identified using Gas Chromatography-Mass Spectroscopy (GCMS). These compounds exhibited potent inhibition against antibiotic resistant bacteria such as Staphylococcus aureus (210P JTU), Psedomonas aeruginosa (ATCC 25619), Klebsiella pneumonia (SR1-TU), Escherchia coli (NI23 JTU) and Streptococcus pneumoniae (SR16677-PRSP) with significant minimum inhibition concentration (MIC) values (25.0-175.0 mg/mL) and minimum bacteriacidal concentrations (MBC) (100.0-500.0 mg/mL). The isolated compounds showed significant antitumor activity against MCF-7, Hela and P388 cell lines. Mahanimbine (3) and essential oil in particular showed potent antibacteria and cytotoxic effect with dose dependent trends (≤5.0 μg/mL). The findings from this investigation are the first report of carbazole alkaloids' potential against antibiotic resistant clinical bacteria, MCF-7 and P388 cell lines.     

Cytotoxic polyacetylenes related to petroformyne-1 from the marine sponge Petrosia sp.

Four polyacetylenes related to petroformyne-1 were isolated from the marine sponge Petrosia sp. Their structures were determined on the basis of spectroscopic data and the modified Mosher analysis. They exhibit cytotoxic activity against P388 murine leukemia cells.     

IMPAIRED ACCUMULATION OF A CATIONIC PHOTOSENSITIZING AGENT BY A CELL LINE EXHIBITING MULTIDRUG RESISTANCE

Abstract —Transport and accumulation of copper benzochlorin iminium salt (CDSl), a cationic photosensitizing agent, were examined using the P388/ADR murine leukemia, which exhibits the MDR (multidrug resistance) phe-notype, and the wild-type parent cell line, P388. The recent availability of radioactive CDSl permitted kinetic studies at drug levels in the submicromolar range. Exclusion of CDSl by P38WADR cells could be demonstrated, indicating that this agent is a substrate for the outward transport system associated with MDR. These results have implications with regard to the efficacy of cationic photosensitizers against this common neoplastic phenotype. The CDSl was readily accumulated by P388 cells and by P388/ADR cells: when the outward transport system was inhibited. Under these conditions, CDSl was tightly bound and could not be washed out even when the outward transport system was reactivated.     

二十二碳六烯酸双氢青蒿素酯的合成及其抗肿瘤活性的初步研究

青蒿素是从菊花科植物黄花蒿中分离得到的一种高效抗疟活性成分,其衍生物双氢青蒿素、蒿甲醚及青蒿琥酯等亦被广泛用于各类疟疾的治疗.     

New Sesterterpenoids from the Marine Sponge Phyllospongia papyracea

Chemical investigation of an extract of the marine sponge Phyllospongia papyracea, collected from the South China Sea, led to the isolation and identification of three new scalarane‐type sesterterpenoids, compounds 1 – 3 . Their structures were elucidated by spectroscopic methods, including 1D‐ and 2D‐NMR as well as high‐resolution ESI‐MS experiments. (12α,16β)‐12‐Acetoxy‐16‐hydroxy‐20,24‐dimethyl‐25‐norscalar‐17‐en‐24‐one ( 1 ) was cytotoxic against the leukemia P388 cancer cell line, with an IC₅₀ value of 5 μg/ml.     

Wrightiamines A and B,two new cytotoxic pregnane alkaloids from Wrightia javanica

Two new pregnane alkaloids, wrightiamines A (1) and B (2), were isolated from the extract of the tropical Apocynaceous plant Wrightia javanica collected in Thailand, and their structures were elucidated by spectral data. Wrightiamine B (2) was preparaed from 3beta-hydroxy-5alpha-pregnan-20-one to establish the configuration of the C-20 position as S. Wrightiamine A (1) exhibited cytotoxic activity against vincristine-resistant murine leukemia P388 cells.     

11‐ and 4′‐Epimers of Chaetomugilin A,Novel Cytostatic Metabolites from Marine Fish‐Derived Fungus Chaetomium globosum

11‐ and 4′‐epichaetomugilin A were isolated from a strain of Chaetomium globosum that was originally isolated from the marine fish Mugil cephalus. 11‐Epichaetomugilin A is the first compound to have an opposite absolute configuration at C(11) to that of other azaphilones isolated to date. Their absolute configurations were elucidated on the basis of spectroscopic analyses, including 1D‐ and 2D‐NMR techniques, and some chemical transformations. 11‐Epichaetomugilin A weakly inhibited the growth of cultured P388 cells and HL‐60 cells (IC₅₀ 88.9 and 66.7 μM , resp.).     

Three new sorbicillin trimers,trisorbicillinones B,C, and D,from a deep ocean sediment derived fungus,Phialocephala sp. FL30r

Eighteen sorbicillonoids, including three new sorbicillin trimers, trisorbicillinones B (2), C (3), and D (4), were isolated from a deep ocean sediment derived fungus, Phialocephala sp. FL30r. Their structures were determined by IR, MS, CD, and NMR spectral data. The cytotoxic activities of the new trisorbicillinones B (2), C (3), and D (4) were tested against both P388 and K562 cell lines.