Acid and base catalyzed intramolecular cyclizations of N-benzoylthioureidoacetal, contain-ing four functional groups adjacent to thiourea such as benzocarbamoyl, acetal, thioure and amide, were investigated. The condensation reaction of N-benzoyl thiocarbamoylgly-cine amide in the presence of 10% aqueous NaOH provided 1-(2,2-dimethoxy)ethyl-imi- dazolidine-2-thione exclusively. In the presence of pyridine, it was transformed to 2- thiohydantoin. N-Benzoyl thiocarbamoyl glycine amide was completely transformed to an iminothiazolidine exclusively in the presence of Lewis acid such as borontrifluoride ether-ate or trimethylsilyl iodide. 1-(2,2-Dimethoxy)ethyl-imidazolidine-2-thione was transformed to imidazole[2,1-b]thiazole and pyrazino[5,1-a]imidazole in the presence of $BF_3$.$ET_2$O and formic acid, respectively.

Stereochemical isomers with hydroxy groups were synthesized by reacting 2-(dimethoxy-methyl)cyclohexanone with propargylmagnesium bromide. The stereo chemical structures were identified by NMR spectral interpretation and the geometry optimization. To assist the NMR interpretation, geometry optimization based on semi-empirical AM1 and PM3 methods was applied. Throughout this study, the structures of the two isomers were all determined and $^{1}H$ and $^{13}C$ NMR spectra were fully assigned. It was proven that the less polar isomer is an axial alcohol and the more polar one is an equatorial alcohol.

A synthetic procedure for the preparation of indole-2,3-dione derivatives 6 as a potential NMDA receptor glycine site antagonist with improved pharmacological profile compared with 2-carboxyindole derivative 5, starting from readily available 3,5-dichloroaniline (7), is described.

Aspirin has been widely used as analgesic and anti-inflammatory drug. Recently, it was elucidated that aspirin have anti-coaggregatory effect in low dose. This study was carried out to investigate the synthesis of aspirin derivatives from aspirin and aromatic compound of antioxidant and its biological activities. Synthesis of aspirin derivatives was prepared by esterification in the presence of 1, 1-carbonyldiimidazole. Biological activities was examined using effect of anti-coagulant on bleeding time, effect of antioxidant and effect of anti-platelet aggregation. As a result, SJ-101 showed strong antioxidative activity and anti-coagulant activity among four compounds. Anti-platelet aggregation of SJ-101 was examined by collagen, ADP, PAF method. SJ-101 exhibited more stronger activity to aspirin at collagen aggregation reaction. These finding demonstrates that SJ-101 is usefull as care drug of aging and old-disease because of its has antioxidant activity, anti-coagulant activity and anti-platelet activity.

Cannabigerol (1, CBG), methyl 4-[(2E)-3,7-dimethyl-2,6-octad ienyl)oxy]-3-methoxybenzoate (2, DTM), 5-fluorouracil (3, FU) as a reference, and cannabidiol (4, CBD) were tested for their growth inhibitory effects against KB(ATCC NO, OCL 17) cell lines using two different assays, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and the sulforhod-amine B protein (SRB) assay. These compounds showed inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antitumor activities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentration range of 1 to 100 M. The comparison of $IC_{50}$ values of these compounds in tumor cell lines showed that their susceptibility to these compounds decreases in the following order: DTM > CBD > 5-FU > CBG by MTT assay and DTM = CBD > 5-FU > CBG by SRB assay. CBG 1, DTM 2, 5-FU 3, and CBD 4 were tested for their cytotoxic effects on NIH 3T3 fibroblasts using two different assays, the MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range against NIH 3T3 fibroblasts. In general, the cytotoxic acivities of these compounds (1, 2, 3 and 4) were dose-dependent over the micromolar concentraion range of 1 to 100 M. The comparison of $CD_{50}$ values of these compounds in NIH 3T3 fibroblasts shows that their susceptibility to these compounds in decreases the following order(:) CBD > 5-FU > DTM > CBG by MTT assay, CBD > 5-FU > CBG > DTM by SRB assay. These results suggest that DTM 2 has the most growth-inhibitory activity against KB cell lines.

In continuation of the previous work (Fathalla, 1992) on the synthesis of some heterocycles containing uracil moiety, we report herein the incorporation of uracil moiety into cyan-opyridine thione, thiosemecarbazone, semicarbazone, cyanopyridine, ami nocyano pyridine, isoxazoline, pyrazoline, pyrimidine, triazolo pyrimidine, pyran, selena and thiazole derivatives which might modify their biological activities. The biological studies revealed that the chemical compound III f showed high molluscicdal activity than other compounds. The profile of the nucleoprotein extracted from chemically (compound IIIc, e, f and g) treated or UV-irradiated B.alexandrina snails did not show appreciable differences when compared to non-treated (native) snails by using SDS-PAGE, where no obvious qualitative or quantitative differences were observed. Immunization of experimental animals with the nucleoprotein extracted from native, chemically (compound III f ＆ g) treated or physically treated B.alexandrina snails induced significant protection against challenge with normal S.mansoni cercariae, as compared to the non-immunized challenged control. As well as , a decrease in the number of granuloma formation and the size range of granuloma was also observed in immunized animals. It is concluded that, compounds III f and g have a potent molluscicidal activity. They also induced chemical modification comparable to that induced by physical treatment in the snail's nucleoprotein, which could possibly be used in immunization against S. mansoni infection.

7- Bromomethylbenz[a]anthracene is a known mutagen and carcinogen. The two major DNA adducts produced by this carcinogen, i.e., $N^2$-(benz[a]anthracen-7-yl methyl)-2'-deoxyguanosine (2, b[a]$a^2$G) and $N^6$-(benz[a]anthracen-7-ylmethyl)-2'-deoxyadenosine (4, b[a]$a^6$/A), as wel 1 as the simpler benzylated analogs,$N^2$-benzyl-2'deoxyguanosine (1, $bn^2$G) and $N^6$-benzyl-2'-deoxyadenosine (3, $bn^6$/A), were prepared by direct aralkylation of 2'-deoxyguanosine and 2'-deoxyadenosine. To determine the site-specific mutagenicity of these bulky exocyclic amino-substituted adducts, the suitably protected nucleosides were incorporated into 16-base oligodeoxyribonucleotides in place of a normal guanine or adenine residues which respectively are part of the ATG initiation codon for the lac Z' \alpha-complementation gene by using an in situ activation approach and automated phosphite triester synthetic methods. The base composition and the incorporation of the bulky adducts into synthetic oligonucleotides were characterized after purification of the modified oligonucleotides by enzymatic digestion and HPLC analysis.

Twelve compounds with lipid peroxidation inhibitory activity were isolated from the stem bark of E. globulus. Their structures were assigned as a new aromatic monoterpene (1) and eleven known compounds, pinoresinol (2), vomifoliol (3), 3,4,5-trimethoxyphenol 1-O-$\beta$-D-(6'-O-galloyl)glucopyranoside (4), methyl gallate (5), rhamnazin (6), rhamnetin (7), eriodictyol (8), quercetin (9), taxifolin (10), engelitin (11), and catechin (12) on the basis of UV, mass, and NMR spectroscopic analyses. These compounds except vomifoliol significantly inhibited lipid peroxidation in rat liver microsome.

Two sesquiterpene endoperoxides, 1S, 4R, 6R-1, 4-endoperoxy-bisabola-2, 10-diene (1), 1R, 4S, 6R-1, 4-endoperoxy-bisabola-2, 10-diene (II), and a sesquiterpene hydroperoxide, 1$\beta$-hydroperoxygermacra-4 (15), 5, 10 (14)-triene (III) were isolated from the aerial parts of Artemisia stolonifera (Compositae). Their chemical structures were assigned by spectral evidences. Compounds I and II exhibited cytotoxicity against five human tumor cell lines with their $\ED_50 values ranging from 0.20 to 5.43 ${\mu}g/m\ell$ and from <0.1 to 0.87 ${\mu}g/m\ell$, respectively.

Bioassay-guided fractionation of Crataegus pinnatifida (Rosaceae) gave two cytotoxic ursane-type triterpenes which were identified as uvaol (1) and ursolic acid (2) by physicochemical and spectroscopic methods. 3-Oxo-ursolic acid (3) was synthesized from ursolic acid (2) by Jones method. The cytotoxic activities of these compounds were tested against murine L1210 and human cancer cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15) in vitro. Compounds 1 and 2 showed moderate cytotoxicities against L1210, whereas they showed weak activities against human cancer cell lines. However compound 3 exhibited potent cytotoxic activities both in murine and in human cancer cell lines.

A new stilbene diglycoside, piceatannol-3, 4'-O-$\beta$-D-diglucopyranoside (I), together with desoxyrhaponticin (II), emodin-1-O-$\beta$-D-glucopyranoside (III), and physcion-8-O-b-D-gluco-pyranoside (IV), were isolated from the rhizomes of cultivated Korean rhubarb rhizomes(Rheum undulatum), Jong DaeWhang, and the structures of 1-IV were identified on the basis of chemical and spectral evidences.

The effects of modifiers such as methanol, water diethylamine in methanol (10 v/v %), and diethylamine in water (10 v/v %) were investigated at three different concentrations (1, 5, and 10 v/v %) of the modifiers in supercritical $CO_2$ (SC-$CO_2$) in order to enhance the supercritical fluid extraction (SFE) efficiency of cephalotaxine from Cephalotaxus wilsoniana Leaves. Among the modifiers employed, methanol basified with diethylamine was found to greatly enhance the extraction efficiency relative to any other modifiers employed. The results suggest that cephalotaxine in plant matrices may be readily changed from SC-$CO_2$-insoluble salt to SC-$CO_2$-soluble free base by basified modifiers. In addition, SC-$CO_2$modified with basified methanol could enhance the extraction efficiency of cephalotaxine more than 30% when compared to the conventional organic solvent extraction.

We have investigated the in vitro cytotoxic effect of liposome-encapsulated N-(phospho-nacetyl)-L-aspartic acid (PALA) against C-26 murine colon cancer cells, and have compared it in this regard to free PALA. Three different PALA-containing liposomal formulations using distearoylphosphatidylcholine (DSPC), distearoylphosphatidylglycerol (DSPG), and polyethyle-neglycol-derivatized distearoylphosphatidylethanolamine (PEG-DSPE) were made and their cytotoxicity was measured. In 72 hr continuous exposure experiment with C-26 cells, the 50% growth inhibitory concentration ($IC_50$) of DSPG-PALA liposome formulation was $0.09\mu\$, which showed about 65-fold more potent than unencapsulated free PALA ($5.1\mu\$). Similar degree of increase in cytotoxicity was also observed in 1 hr exposure experiment. However the $IC_50$ of PEG-DSPE-PALA liposome and DSPC-PALA liposome were $10.7\mu\$and $11.8\mu\$respectively, which showed slightly less potent than unencapsulated free PALA. Physical characteristics of PALA-liposomes, such as the size and drug:lipid ratio were also determined. In conclusion, negatively-charged DSPG-PALA liposome showed the highest cytotoxic effect among tested on the C-26 cells in vitro.

The relationship between the metabolites of glycyrrhizin (18$\beta$-glycyrrhetinic acid-3-O--D-glu-curonopyranosyl-($1{\rightarrow}2$)-$\beta$-D-glucuronide, CL) and their biological activities was investigated. By human intestinal microflora, CL was metabolized to 18$\beta$-glycyrrhetinic acid (GA) as a main product and to 18$\beta$-glycyrrhetinic acid-3-O-$\beta$-D-glucuronide (GAMG) as a minor product. The former reaction was catalyzed by Eubacterium L-8 and the latter was by Streptococcus LJ-22. Among GL and its metabolites, GA and GAMG had more potent in vitro anti-platelet aggregation activity than GL. GA also showed the most potent cytotoxicity against tumor cell lines and the potent inhibitory activity on rotavirus infection as well as growth of Helicobacter pylori. GAMG, the minor metabolite of GL, was the sweetest.

In order to study the simultaneous determination of (+)- and (-)-cetirizine in human urine we have developed a chiral separation method by HPLC. A chiral stationary phase of $\alpha$$_1$-acidglycoprotein, the AGP-CSP was used to separate the enantiomers. The pH of the phosphate buffer, as well as the content of the organic modifier in the mobile phase, markedly affected the chromatographic separation of (+)- and (-)-cetirizine. A mobile phase of 10 m㏖/1 phosphate buffer (pH 7.0)-acetonitrile (95 : 5, v/v) was used for the urine assays. Ultraviolet absorption was monitored at 230nm and roxatidine was employed as the internal standard for quantification. (+)-Cetirizine, (-)-cetirizine and the internal standard were eluted at retention times of 12, 16, and 32 mins, respectively. The detection limit for cetirizine enantiomers was 400 ng/$m\ell$ of urine. A pharmacokinetic study was conducted with the help of 5 healthy female volunteers who were administered with a single oral dose of racemic cetirizine (20 mg). The peak area ratios provided by the cetirizine enantiomers were linear(r>0.997) over a concentration range of 2.5-200 ${\mu}g/ml$. The peak of the excreted cetirizine enantiomers appeared in the urine sample during the period of 1-2 hrs following the administration of the oral dose. The excreted level of (+)-cetirizine was slightly higher than (-)-cetirizine but the difference was not statistically significant. However, this method appears to have applications for enantioselective pharmacokinetic studies of racemic drugs.

Chondroitin sulfates proteoglycans were isolated from human placenta. For the identification of enzymatic digestion products of isolated proteoglycan, strong anion exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitin ABC and chondroitin B lyase, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-($\beta$-D-gluco-4-enepyranosyluronic acid)-D-galactose ($\delta$Di-OS), 2-acetamide-2-deoxy-3-O-($\beta$-D-gluco-4-enepyranosyluronic acid)-6-O-su lfo-D-galactose ($\delta$Di-6S) and 2-acetamide-2-deoxy-3-O-($\beta$-D-gl uco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose ($\delta$Di-4S) were produced from the human placenta proteoglycan. The anticoagulant activity of chondroitin sulfate proteoglycan was evaluated by activated partial thromboplastin time (aPTT) assay and thrombin time (TT) assay. The clotting times of aPTT and TT were increased from 72 to 144 sec and 19 to 27 sec, respectively. The Immune-modulating activity of chondroitin sulfate proteoglycan was examined by cell proliferation assay and these results suggest that it may play a role in suppression of the function of immune-related cells.

Nucleotide sequence extending 2,3-dihydroxybiphenyl 1,2-dioxygenase gene (pcbC) and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase gene (pcbD) of Pseudomonas sp. DJ-12 was previously analyzed and the two genes were present in the order of pcbD-pcbC preceded by a promoter from Pseudomonas sp. DJ-12. In this study, a 3.8-kb nucleotide sequence located downstream of the pcbC gene was analyzed to have three open reading frames (ORFs) that are designated as orf1, pcbE and orf2 genes. All of the ORFs were preceded by each ribosome-binding sequence of 5-GGAXA-3 (X=G or A). However, no promoter-like sequence and transcription terminator sequence were found in the analyzed region, downstream of pcbC gene. Therefore, the gene cluster appeared to be present in the order of pcbD-pcbC-orf1-pcbE-orf2 as an operon, which is unique organization characterized so far in biphenyl- and PCB-degrading bacteria. The orf1 gene was composed of 1,224 base pairs which can encode a polypeptide of molecular weight 44,950 containing 405 amino acid residues. A deduced amino acid sequence of the orf1 gene product exhibited 21-33％ identity with those of indole dioxygenase and phenol hydroxylase components. The pcbE gene was composed of 783 base pairs encoding 2-hydroxypenta-2,4-dienoate hydratase involved in the 4-chlorobiphenyl catabolism. The orf2 gene was composed of 1,017 base pairs encoding a polypeptide of molecular weight 37,378 containing 338 amino acid residues. A deduced amino acid sequence of the orf2 gene product exhibited 31％ identity with that of a nitrilotriacetate monooxygenase component.