Actinolactomycin,a New 2-Oxonanonoidal Antitumor Antibiotic Produced by Streptomyces flavoretus 18522,and its Inhibitory Effect on the Proliferation of Human Cancer Cells

Actinolactomycin 1, a new 2-oxonanonoidal antitumor antibiotic, was isolated from the fermentation broth of Streptomyces flavoretus 18522 through a bioassay-guided separation procedure. The structure of 1 was determined as 4,7-dihydroxy-3,9-dimethyl-2-oxonanone by the spectroscopic methods. Compound 1 inhibited the proliferation of A2780, K562, HCT-15, A549 and HeLa cells with the IC50 values of 1.4 ± 0.4 μmol/L, 8.4 ± 4.7 μmol/L, 9.4 ± 2.2 μmol/L, 15.4 ± 5.6 μmol/L and 13.7 ± 2.0 μmol/L, respectively. Flow cytometric analysis indicated that 1 could inhibit the cell cycle of tsFT210, A2780 and K562 cells mainly at the G0/G1 phase and could also induce apoptosis in K562 cells.

Identification of Taxus cuspidata Sieb. et Zucc. endophytic fungi-new species, species known and their metabolite

A total of 94 isolates of endophytic fungi were isolated from the bark of 200-yr.-old Taxus cuspidata Sieb. et Zucc.in the primeval forest of the Changbai Mountain Natural Reserve, and 19 species of endophytic fungi were identified, including 10 new recorded-genus-species, 2 new species (Phomopsis Iongiscoleosporu Y. Xiang et Lu An Guo Wu Wen Fang, Coniothyrium macrospoum Y. Xiang J.X. et Lu An Guo Wu Wen Fang), 1 new varied species (Alternaria alternata (Fr.) Keissler var. taxi Y.Xiang et Lu An Guo) and 6 known species of China (Eurotium amstelodomi Mgngin, Eurotium repens de Bary, Botrytis sp.,Penicillium citrinum Thom, Epicoccum nigrium LinK, Fusarium sp.). Through thin layer chromatography (TLC), liquid fermentation metabolite of the strains was determined, and four strains (Alternaria alternata (Fr.) Keissler var. taxi Y. Xiang et Lu An Guo Wu Wen Fang, Botrytis sp., Eurotium amsteloodomi Mgngin, Eurotium repens de Bary) were screened out, whose metabolites reacted positively with the vanillic aldehyde that was one special taxoid developer. Among the four strains, Alternaria alternata (Fr.) Keissler var. taxi Y. Xiang et Lu An Guo, produced one compound largely, which positively reacted with one alkaloids developer-Bismuth potassium iodide. The compound is identified as taxoids type through spectrum analysis. This demonstrates that Alternaria alternata (Fr.) Keissler var. taxiY. Xiang et Lu An Guo can highly produce taxoids largely.

Time-and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid

AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and $100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied. RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit~ L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release. CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

New Metabolites of Aconitine in Rabbit Urine

A sensitive analytical method to identify and determine aconitine and its metabolites in rabbit urine was developed by liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MSn).In this method,aconitine and its four metabolites in rabbit urine were isolated and deduced As 16-O-demethylaconine(M1), benzoylaconine(M2), 16-O-demethylbenzoylaconine (M3)and aconine(M4).M1 and M3 are new metabolites of aconitine and M2 and M4 are first identified in rabbit urine.

Two Phaeophytin Type Analogues from Marine Sponge Dysidea sp.

A new compound named 13b (S )-hydroxy-17c-ethoxypheaophorbide a (2) together witha known compound 17c-ethoxypheaophorbide a (1) were isolated from marine sponge Dysidea sp.collected in South China sea. The structures were elucidated by spectroscopic analysis as well ascomparison with those reported in literatures.

Determination of Clarithromycin in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry： Validation and Application in Clinical Pharmacokinetic Study

Aim To develop a liquid chromatographic-tandem mass spectrometric (LC-MS-MS)method to determine clarithromycin in human plasma. Methods The analyte and internal standardroxithromycin were extracted from plasma samples by n-nexane-dichloromethane-isopropanol(300:150:15, V/V/V) and chromalographed on a C_(18) column. The mobile phase consisted ofmethanol-water-formic acid (80 = 20:1, V/V/V) . Detection was performed on a triple quadrupoletandem mass spectrometer via electrospray ionization source (ESI) in the positive mode. Results Themethod had a lower limit of quantification of 10.0 ng·mL^(-1) when 0.2 mL plasma was used. Thelinear calibration curves were obtained in the concentration range of 10.0 - 5000 ng·mL^(-1) . Theintra- and inter-run precisions were lower than 3.3% in terms of relative standard deviation (RSD),and the accuracy ranged +- 0.7% in terms of relative error (RE). T_(max), C_(max), T_(1/2) andAUC_(0-24h), values were found to be (3.1 +- 2.7)h, (8 750+-4734) ng·mL^(-1), (5.3+-2.2) h, and(5932+-2449)ng·mL^(-1), respectively, after a single oral dose of 250 mg clarithromycin tablet to18 volunteers. Conclusion This validated method was successful in the evaluation of phaimacokineticprofiles of clarithromycin tablets administered to 18 healthy male volunteers.

Biphenyl Ferulate from Glehnia littoralis

From the underground parts of Glehnia littoralis Fr. Schmidt ex Miquel (Umbelliferae), a new compound named glehnilate was obtained. Its structure was determined by analysis of its spectral data.

A New Steroidal Saponin from Dioscorea deltoidea Wall var. orbiculata

Bioactivity-guided fractionation led to the isolation of a new steroidal saponin, orbiculatoside B, together with a pair of furostanol saponins, protobioside and methyl protobioside, from the fresh rhizomes of Dioscorea deltoidea Wall var. orbiculata. The new compound was identified to be isonarthogenin 3 O - a - L - rhamnopyranosyl (12) - [ a - L - rhamnopyranosyl - ( 1 4 ) ] - b - D - glucopyranoside by various NMR techniques in combination with chemical methods. The three saponins showed strong activity against Pyricularia oryzae, and were cytotoxic to cancer cell line K562, HCT-15, A549, and A2780a in vitro.

Two New C-glucoside Flavonoids from Leaves of Crataegus pinnatifida Bge.var.major N.E.Br.

Two new C-glucoside flavonoids, namely 8-C-b-D-(2-O-acetyl) glucofuranosyl apigenin and 3-O-acetylvitexin, were isolated from leaves of Crataegus pinnatifida Bge. var. major N. E. Br.. Their structures were elucidated by the spectroscopic means and chemical evidence.

Metabolites of A Novel Antibiotic Bitespiramycin in Rat Urine and Bile

A sensitive analytical method to identify active metabolites of bitespiramycin in rat urine and bile was developed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MSn). Bitespiramycin and its major active metabolites in rat urine and bile were isolated and identified as Ml serial (spiramycin Ⅰ, Ⅱ, Ⅲ), M2 serial (platenomycin Al, josamycin and leucomycin Al) and M3 serial (deisovalerylplatenomycin Al, deisovaleryl-josamycin, deisovalerylleucomycin Al).

Characterization of a novel toxin-antitoxin module,VapBC,encoded by Leptospira interrogans chromosome

Comparative genomic analysis of the coding sequences (CDSs) of Leptospira interrogans revealed a pair of closely linked genes homologous to the vapBC loci of many other bacteria with respect to both deduced amino acid sequences and operon organizations. Expression of single vapC gene in Escherichia coli resulted in inhibition of bacterial growth,whereas co-expression of vapBC restored the growth effectively. This phenotype is typical for three other characterized toxin-antitoxin systems of bacteria, i.e., mazEF[1], relBE[2] and chpIK[3]. The VapC proteins of bacteria and a thermophilic archeae, Solfolobus tokodaii, form a structurally distinguished group of toxin different from the other known toxins of bacteria. Phylogenetic analysis of both toxins and antitoxins of all categories indicated that although toxins were evolved from divergent sources and may or may not follow their speciation paths (as indicated by their 16s RNA sequences), co-evolution with their antitoxins was obvious.

A New Biflavonoid from Stellera chamaejasme L.

A new biflavonoid, stelleranol, was isolated from the roots of Stellera chamaejasme L.. Its structure was determined by the analysis of MS and NMR data, especially 2D NMR spectra.

High-Performance Liquid Chromatographic Method for Determination of Germacrone in Rat Plasma

Aim A reliable high-performance liquid chromatographic (HPLC) method wasdeveloped for determination of germacrone in rat plasma. Methods The plasma samples were treatedwith acetonitrile and analyzed by HPLC with UV detection at 244 nm. Results The limit of detectionwas 100 ng·mL^(-1) for germacrone in plasma and the linear range was 0.1004-15.06 μg·mL^(-1) inplasma. The RSD of intra-day and inter-day assay was 1.87% - 4.29% and 1.29% -5.15%, respectively.The recoveries of germacrone were over 95%. The endogenous substances in plasma did not show anyinterference in the analysis. Conclusion The method is accurate and convenient, and suitable forpharmacokinetic studies of germacrone in rats.

One New A-type Proanthocyanidin Trimer from Lindera aggregata(Sims) Kosterm.

One new A - type proanthocyanidin trimer, lindetannin trimer, was isolated from the stems of Lindera aggregata (Sims) Kosterm.. Its structure was elucidated by spectral and chemical methods.

A New Glucuronidated Metabolite of Andrographolide in Human

A new andrographolide metabolite 1 was isolated from human urine samples after oral administration. The structure was determined to be 3-carbonylandrographolide-19-O-β-D-glu- curonide on the basis of chemical evidences and spectral analysis, especially by 2D-NMR techni- ques.

In Vitro Skin Permeation of Osthol from Hydro-Alcoholic Gel Formulations

Aim To evaluate the in vitro percutaneous absorption behavior of osthol from a series of hydro-alcoholic gel formulations containing three penetration enhancers through excised human skin (stratum cormeum and epidermis,SCE). Methods Excised human skin was mounted in Franz-type diffusion cells. The samples withdrawn from the receptor cell were analyzed for osthol content by high-performance liquid chromatography (HPLC). Results The enhancers azone,menthol and chenopodium increased the osthol percutaneous steady-state fluxes 3.12, 2.00 and 1.25 times those of the enhancer-free formulations (controls), separately. Conclusions The main enhancement mechanism of the skin penetration enhancers azone, menthol and chenopodium is to destroy the barrier function of stratum corneum, reducing the resistance of drug transport through the skin and increasing the diffusion coefficients of osthol.

Design and Synthesis of New Arylsulfonamide and Arylamide Derivatives for the Platelet Aggression Inhibitor

A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggregation were tested in vitro by using the Born test on rabbits.

Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E1

Aim To study the effect of complexation with hydroxylpropyl-β-cyclodextrin(HP-β-CD) on the solubility, dissolution rate and chemical stability of prostaglandin E_1 (PGE_1) ,thereby providing a basis for preparing a stable solid or aqueous preparation of PGE_1 formulatedwith HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE_1 was studied by phasesolubility method. The formation of inclusion complexes of PGE_1 with HP-β-CD in the aqueoussolution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid stateby IR spectra and X-ray diffractome-try. An solid inclusion complex of PGE_1 with HP-β-CD wasprepared by lyophilization. The dissolution rate and stability of the inclusion complex weredetermined and compared with those of PGE_1 alone. Meanwhile, the stability of PGE_1 aqueoussolutions in the presence of HP-β-CD was studied under different pH conditions. Results Thesolubility of PGE_1 increased linearly with increasing HP-β-CD concentration in various pH bufferedsolutions, showing typical A_L-type phase solubility diagrams. The stability and dissolution rateof the solid inclusion complex of PGE_1 were significantly increased, compared with those of purePGE_1 . The stability of PGE_1 in HP-β-CD solutions was also obviously improved under acidic andbasic conditions, but the stabilizing effect was absent under neutral conditions. Conclusions Thesolubility,dissolution rate and chemical stability of PGE_1 are markedly improved by complexationwith HP-β-CD: It is quite possible to prepare a stable PGE_1 inclusion complex-containing soliddosage forms, but almost impossible to obtain a stable aqueous preparation of PGE_1 formulated withHP-β-CD.

A New Isomalabaricane Triterpenoid from Sponge Jaspis sp.

From the marine sponge Jaspis sp., a new isomalabaricane triterpenoid 22, 23- dihydrostellettin D (1) was isolated, and its structure was established on the basis of IR, MS and extensive 2D NMR spectroscopic analysis. It is a unique skeleton compound rarely obtained from Chinese marine organisms.

Two New Cycloartane Triterpenes from The Leaves of Quercus valiabilis Blume

Two new cycloartane triterpenes were separated from the leaves of Quercus valiabilis Blume. The structures were identified as 4α,14α-dimethyl-9β,19-cycloergost-3α-yl-24-one and 4α,14α-dimethyl-9β,19-cycloergost-24(24′)-en-3α-yl-acetate.