JPH11193295A - Beta-d-xylopyranoside-based compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound consisting of a specified β-D- xylopyranoside-based compound, having heparan sulfate and/or heparin elongation activity and useful as e.g. a medicine having antiproliferative activity specifically against cancerized and transformed cells. SOLUTION: This compound is a new hydroxynaphthyl-β-D-xylopyranoside based compound represented by the formula [(n) is an integer of >=1] [e.g. O(6-hydroxy-2-naphthyl)-β-xylopyranosidel and has heparan sulfate and/or heparin elongation activity, antiproliferative activity selectively against cancerized and transformed cells and no effect on proliferation of normal cells and therefore is expected to be useful as a medicine or the like. This compound is obtained by the process in which a reaction product of 2,3,4-tri-o-benzyl-D-xylopyranose with phenyl isocyanate is reacted with 2,6-dihydroxynaphthalenemonobenzoate and then trimethylsilyltrifluoromethanesulfonate is dripped thereto to carry out further reaction.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel β-D-xylopyranoside compound, and more particularly, to hydroxynaphthyl-β-D-, which has a strong cell growth inhibitory effect on abnormally growing cancerous cells. The present invention relates to a xylopyranoside compound.

[0002]

2. Description of the Related Art Proteoglycan is a macromolecular substance in vivo in which a glycosaminoglycan chain is bound to a core protein. In vivo, the proteoglycan is an intracellular granule, a cell membrane surface, or an extracellular matrix such as connective tissue or basement membrane. It is widely distributed. Glycosaminoglycans are classified into chondroitin sulfate / dermatan sulfate and heparan sulfate / heparin based on their sugar chain skeletons, and their physiological roles are considered to be significantly different.

[0003] The sugar chain fine structure of the glycosaminoglycans of both systems greatly varies depending on the species, cell type, age, and anatomical site. It is thought to function as an essential regulator of important physiological functions such as cognitive ability, ability to select proteins of the basement membrane such as kidney, and blood anticoagulant action. However, the binding region of glycosaminoglycan to the core protein is common to all proteoglycans, and a tetrasaccharide (xylose → galactose → galactose →) having D-xylose β-linked to a serine residue of the core protein at the reducing end is used. Glucuronic acid).

[0004] It is also known that heparin suppresses the growth of vascular smooth muscle cells, and that certain heparan sulfate and dermatan sulfate suppress the growth of certain normal fibroblasts (J. Cell Physiol). .147,523-530,1991). However, in order to exhibit the growth inhibitory effect, it is necessary to add a large amount of these glycosaminoglycans from outside.

Conventionally, a β-D-xylopyranoside compound having a p-nitrophenyl group or the like as an aglycone functions as an initiator for elongating a glycosaminoglycan chain not via a core protein, thereby altering the amount of endogenous proteoglycan biosynthesis. Is known to greatly alter the properties of certain cell membrane surfaces (see, for example, J. Biochem., 74, 1069-1073,
1973). For this reason, there has been proposed an idea to design various amphipathic glycosides having hydrophobic aglycones such as phenyl group and alkyl group, and to administer them to cells and living bodies to disrupt proteoglycan biosynthesis. (JP-B 63-61308, JP-B 1-36-833, JP-B 4-25254). Furthermore,
Numerous xylose derivatives in which the aglycone moiety has been organically synthesized have been synthesized and used as a glycosaminoglycan synthesis initiator or as a proteoglycan biosynthesis disruptor (for example, Biochem. J., 24, 1,591). -60
1,1987, JP-B 63-60748).

[0006]

However, glycosaminoglycan chains extended using these xylose derivatives having aglycones are only chondroitin sulfate and dermatan sulfate, and heparan sulfate and heparin having different sugar chain skeletons are not available. It has not been synthesized at all. In recent years, it has been found that β-D-xylopyranoside, in which aglycone is substituted by a condensed ring compound such as estradiol or 2-naphthol, clearly exhibits a synthesis initiation activity for heparan sulfate (J, Biol. Chem. , 266,6674-6677,199
1; Glycobiology, 2,492, 1992; J, Biol. Chem., 269, 300-3
07, 1994; WO94 / 05678).

[0007] However, these β-D-xylopyranosides still have a much higher initiation activity for chondroitin sulfate / dermatan sulfate than heparan sulfate, and have high cytotoxicity and solubility in water. However, there were inconveniences such as low dose and limited dose concentration. In addition, it has been pointed out that they show heparan sulfate elongation activity only in certain cell lines. Therefore,
The present inventors focused on the hydrophilicity of aglycone, and considered that if the hydrophilicity of aglycone was appropriately increased, the affinity of xylopyranoside for cells would change, and it would efficiently reach the heparan sulfate biosynthesis site (Golgi apparatus). Based on the above, the present inventors have made intensive studies on a compound using an aglycone having a hydrophilic group introduced therein, and have found that xylopyranoside using a specific aglycone having a hydroxyl group exhibits heparan sulfate elongation activity.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel β-D-xylopyranoside compound which is useful as a medicament having heparan sulfate / heparin elongation activity widely. That is, the gist of the present invention resides in a hydroxynaphthyl-β-D-xylopyranoside compound represented by the following general formula (1). In the formula, n is an integer of 1 or more.

[0009]

Embedded image

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. The compound of the present invention is a hydroxynaphthyl-β-D-xylopyranoside compound represented by the general formula (1). In the above formula, the hydroxynaphthyl group glycosidically bonded to D-xylopyranose is usually a 1-naphthyl group or a 2-naphthyl group glycosidically bonded at the 1- or 2-position of the naphthalene ring. It has a structure in which at least one of the hydrogen atoms at the 1- to 8-positions is substituted with a hydroxyl group, and a 2-naphthyl group is preferred. The number n of the hydroxyl groups that can be contained in the naphthalene ring is 1 or more, usually 1 to 3, but 1 is preferred. The hydroxyl group may be present on any of the two aromatic rings of the naphthalene ring.

Specific examples of the hydroxynaphthyl group include:
For example, 6-hydroxy-2-naphthyl, 4-hydroxy-2-naphthyl, 8-hydroxy-2-naphthyl, 3-
Monohydroxynaphthyl groups such as hydroxy-1-naphthyl, 5-hydroxy-1-naphthyl and 7-hydroxy-1-naphthyl; 4,6-dihydroxy-2-naphthyl;
4,8-dihydroxy-2-naphthyl, 6,8-dihydroxy-2-naphthyl, 3,5-dihydroxy-1-naphthyl, 3,7-dihydroxy-1-naphthyl, 5,7
A dihydroxynaphthyl group such as dihydroxy-1-naphthyl; 4,6,8-trihydroxy-2-naphthyl;
And a trihydroxynaphthyl group such as 3,5,7-trihydroxy-2-naphthyl. Of these, a monohydroxynaphthyl group, particularly a 6-hydroxy-2-naphthyl group, is preferred.

Specific compounds include O (6-hydroxy-2-naphthyl) -β-D-xylopyranoside O (4-hydroxy-2-naphthyl) -β-D-xylopyranoside O (8-hydroxy-2-naphthyl) ) -Β-D-xylopyranoside O (3-hydroxy-1-naphthyl) -β-D-xylopyranoside O (5-hydroxy-1-naphthyl) -β-D-xylopyranoside O (7-hydroxy-1-naphthyl)- β-D-xylopyranoside and the like.

The xylopyranoside compound represented by the general formula (1) of the present invention can be basically synthesized by a glycosylation method known per se. For example,
After protecting the hydroxyl groups at the 2-, 3- and 4-positions of D-xylose with acetic anhydride, benzyl chloride or the like with a protecting group such as an acetyl or benzyl group, the 1-position is treated with an aluminum halide such as aluminum chloride or aluminum bromide. Alternatively, it is activated by halogenation or phenylcarbamoylation with phenyl isocyanate or the like. That is, a leaving group such as halogen or phenylcarbamoyl is introduced. The desired compound is obtained by reacting a naphthalene having one or more hydroxyl groups other than one hydroxyl group of naphthalene having two or more hydroxyl groups protected with a protecting group such as a benzoyl group, and then removing the protecting group. be able to. The removal of the protecting group is carried out in two steps according to a conventional method. For example, the benzoyl group of the naphthalene ring can be eliminated by sodium methoxide (NaOMe), and the benzyl group of the xylopyranose ring can be eliminated by catalytic hydrogenation. The glycosylation reaction may be affected by the type of protecting group or leaving group of xylose, the number of hydroxyl groups on the naphthalene ring, the degree of nucleophilicity by the type of protecting group, etc., and furthermore, the reactant, the solvent, etc. It is preferable that the optimum reaction conditions are appropriately confirmed experimentally and selected according to the type of xylose and hydroxy-substituted naphthol used. The reaction product thus obtained can be purified by a conventional purification method such as a recrystallization method for crystallizing from methanol or the like, or a chromatography method.

The hydroxynaphthyl-β-D-xylopyranoside represented by the general formula (1) of the present invention (hereinafter referred to as Xyl-N
Sometimes abbreviated as apOH. The) compound exhibits a cell growth inhibitory action as shown in the test examples described later, and exhibits a particularly remarkable effect on transformed cells and cancerous cells. In addition, the compound Xyl-NapOH of the present invention exhibits not only the elongation of chondroitin sulfate / dermatan sulfate chains, but also the activity of elongating heparan sulfate chains widely. The optimal concentration ranges of the cell growth inhibitory action and the heparan sulfate chain elongation action are in agreement. Furthermore, known Op-nitrophenyl-β-D-xylopyranoside, which has no elongation activity only to chondroitin sulfate / dermatan sulfate chains, and O-hydroxynaphthyl-β-L-xylopyranoside, which has no glycosaminoglycan elongation activity, are cells It had no effect on growth. Also,
The known O 2-naphthyl-β-D-xylopyranoside is
HO cells have heparan sulfate elongation activity (J. Biol. Che.
m., 269, 300-307, 1994), however, did not show heparan sulfate elongation activity or cell growth inhibitory activity against these transformed cells or cancerous cells.

The functions of heparan sulfate include stabilization of growth factors and regulation of its activity, which means that heparan sulfate biosynthesis manipulates cell proliferation. Compared to normal cells, transformed cells and cancerous cells were more sensitive to Xyl-NapOH of the present invention and several times more vigorous in growth inhibition effect because Xyl-NapOH is an endogenous essential for growth. Heparan sulfate-suppresses the biosynthesis of proteoglycan, has the effect of interfering with the signal transmission from the growth factor receptor, or the heparan sulfate chain extended from xyloside directly antagonizes the biosynthesis of endogenous heparan sulfate-proteoglycan, It is presumed to have an action of suppressing cell proliferation. In any case, it is considered that the Xyl-NapOH of the present invention produces a heparan sulfate variant having an antiproliferative action by a mechanism not previously considered. It seems to show a particularly remarkable growth inhibitory effect on transformed cells and cancer cells that self-grow by the autocrine mechanism.

As described above, the Xyl-NapOH of the present invention has a heparan sulfate chain elongation effect on many animal cells including humans. And it became clear that it showed a strong strong cell growth inhibitory action on abnormally proliferating cancerous cells without showing a very strong cell growth inhibitory action on normal cells.
This suggests that it may be a highly safe drug that acts only on abnormal sites. Thus, for example, cancer inhibitors or diseases caused by abnormal cell proliferation, such as arteriosclerosis caused by proliferation of vascular smooth muscle cells, vascular occlusion, or chronic synovium caused by abnormal proliferation of joint synovial cells or immune cells. It is expected to be effective as a drug for suppressing rheumatism, leukemia hatred, and sarcoma growth.

[0017]

The β-D-xylopyranoside having a hydroxynaphthyl group represented by the general formula (1) of the compound of the present invention has a known O 2 -naphthyl-β-D-xylopyranoside having an activity of initiating heparan sulfate biosynthesis. It has the activity to elongate heparan sulfate even for cell types that do not have it. Moreover, the compound of the present invention has a growth inhibitory activity selectively on cancerous cells and transformed cells, and has a property of not affecting growth on normal cells. It is expected.

[0018]

EXAMPLES The present invention will be described in more detail with reference to the following Examples and Test Examples, but the present invention is not limited thereto without departing from the gist thereof.

Example 1 Synthesis of xylopyranosides (1) O (6-human peroxy-2-naphthyl) -β-D-xyloperanosit (D-Xyl-Na
Synthesis of p (6) OH) 2,3,4-tri-O-benzoyl-D-xylo-pyranose and 2,3,4-tri-O-benzoyl-1-O-phenylcarbamoyl-β obtained from phenylisocyanate -D-xyloperanose (2.3 g; 4.3 mmol) and 2,6-dihydroxyperoxynaphthalene monobenzoate (1.15 g; 4.36 mmol) were added to dichloromethane containing molecular sieve 4A (3 g). After stirring at room temperature for 1 hour, the mixture was added with trimethylsilyl trifluoromethanesulfonate (0.85m
1, 1.03 eq.) was added dropwise. After stirring for 1.5 hours as it was, the mixture was filtered, and the filtrate was washed with a saturated aqueous solution of sodium hydrogen carbonate and water, and dried over MgSO ₄ . After evaporating the solvent under reduced pressure, the residue was recrystallized from ethanol, and O (6-O-benzene-2-naphthyl) -2,3,4-tri-O-benzene-β-D-xylohyranosit (1.27 g; yield 45) %). The protecting group is removed in two steps by a conventional method, and the desired O (6-human-peroxy-2-naphthyl) -β-D-xylo-peranocit (3
80 mg; 63% yield). Nuclear magnetic resonance spectrum: ¹ H-NMR (400 MHz, CD ₃ OD) δ _H (pp
m) = 7.53-6.92 (m, 6H, aromatic-H), 4.83 (d, 1HJ _1.2 = 7.3H
z, H-1), 3.85 (dd, 1HJ _{5eq, 4 =} 4.9Hz, J _{5eq, 5ax =} 11.2Hz, H-5e
q), 3.52-3.27 (m, 4H). Optical rotation: -25.8 ° (c = 0.1; CH ₃ OH), melting point: 240 ° C.
(Decomposition point).

(2) Synthesis of O (6-human-peroxy-2-naphthyl) -β-L-xylo-hyperanosit (L-Xyl-Nap (6) OH) 2,3,4-tri-O-phenicyl-L-xylo 2,3,4-Tri-O-benzoyl-1-O-phenylcarbamoyl-β-L-xylo-pyranose (2.04 g; 3.78 mmol) obtained from peranose and phenyl isocyanate, and 2,6-dihydroxy-hydroxynaphthalene monobenzoate (1.0%) g; 3.78 mmol) was added to dichloromethane containing molecular sieve 4A (3 g). After stirring at room temperature for 2 hours, the mixture was cooled to -78 ° C under a nitrogen atmosphere, and trimethylsilyltrifluoromethanesulfonate (0.75
ml, 1.0 eq.) was added dropwise. After stirring at −78 ° C. for 18 hours, the mixture was returned to room temperature, the mixture was filtered, and the filtrate was washed with a saturated aqueous solution of sodium hydrogen carbonate and water, and dried over MgSO ₄ . After evaporating the solvent under reduced pressure, recrystallization from methanol
(6-O-benzene-2-naphthyl) -2,3,4-tri-O-benzoyl-β-L-xylohyranosit (1.42 g; yield 56%) was obtained. The protecting group is removed in two steps by a conventional method, and the desired O (6-human peroxy-2-naphthyl) -β-L
-Xyloperanosit (522 mg; 78% yield) was obtained. Nuclear magnetic resonance spectrum: ¹ H-NMR (400 MHz, CD ₃ OD) δ _H (pp
m) = 7.53-6.93 (m, 6H, aromatic-H), 4.84 (d, 1HJ _1.2 = 7.3H
z, H-1), 3.86 (dd, 1HJ _{5eq, 4 =} 4.9Hz, J _{5eq, 5ax =} 11.2Hz, H-5e
q), 3.51-3.25 (m, 4H). Optical rotation: + 25.7 ° (c = 0.1; CD ₃ OD), melting point: 240 ° C.
(Decomposition point).

(3) Synthesis of other xylopyranoside compounds According to the method of Fritz et al. (J. Biol. Chem., 269, 300-307, 1994), O 2-naphthyl-β-D-xylopyranoside (Xyl- Nap), Op-nitrophenyl-β-D-xylopyranoside (Xyl-PheNO ₂ ) was synthesized.

Test Example 1 Influence of Xylopyranoside Compounds on Cell Proliferation Various normal and cancerous cultured cells including humans (human lung fibroblasts, human lung carcinoma cells, mouse 3T3 fibroblasts, SV-40-transformed 3T3 cells) , Human umbilical vein endothelial cells, and human umbilical vein transformed endothelial cells) were collected by detachment with trypsin, and F-12 containing insulin (10 ng / ml), transferrin (25 ng / ml) and 10% fetal bovine serum.
Suspended in medium (Sigma). Each 3000-5000 cells were transplanted into a 96-well microculture dish, cultured for 4 hours, and then depleted of serum and cultured for 24 hours. Then, in the presence of various concentrations of O (6-hydroxy-2-naphthyl) -β-D-xylopyranoside (D-Xyl-Nap (6) OH) or other xylopyranoside compounds synthesized in Example 1, 10 ng / l. Cells were grown by adding ml of epidermal growth factor (EGF; Genzyme, Cambridge, MA). However, human umbilical vein endothelial cells were grown by adding 20% human serum.

As a control, a culture without the addition of a growth factor and a culture with the same concentration of the solvent (dimethyl sulfoxide: DMSO) used for dissolving the xylopyranoside as the sample were also carried out. After culturing for 72, 96 and 120 hours, the cells are fixed with glutaraldehyde and the nuclei of the cells are crystal violet (Merck, Darmstadt, FRG)
Stained. After washing away excess dye, Triton X-100
(Rohm & Haas) solution for 24 hours to dissolve the fixed cells, and measure the amount of dye bound to the cells by measuring the absorbance at 600 nm with a microplate reader (Titertek multiscan) to determine the number of cells. . The result is DMSO
Was calculated after correcting for the influence of.

The results are shown in FIGS. Growth of many cells was inhibited in the presence of D-Xyl-Nap (6) OH in a dose-dependent manner. However, transformed cells and cancer cells were more sensitive to xylopyranoside than normal cells and were more strongly inhibited. For example, E for 96 hours of processing
Compared with D ₅₀ values, human lung-derived carcinoma cells 3-4-fold more sensitive is higher than in normal human lung fibroblasts (Fig. 1: 1-a and 1-b). Also, the SV-40 transformed 3T3 cells were 6-7 times more sensitive than the 3T3 cells before transformation (FIG. 2: 1-c and 1-d). Umbilical vein-derived endothelial cells showed a reduced proliferation rate at very low concentrations of xylopyranoside, but at higher concentrations the proliferation rate was not significantly reduced (FIG. 3: 1-e).
In contrast, the transformed umbilical vein endothelial cells were three times more sensitive (FIG. 3: 1-f). In general, after 96 hours of exposure to 0.15-0.2 mM D-Xyl-Nap (6) OH, transformed cells were completely inhibited from growing, whereas normal cells were 50% or less. It was only inhibitory.

The stereoisomer O (6-hydroxy-2)
-Naphthyl) -β-L-xyloside (L-Xyl-Nap (6) OH), human lung fibroblasts (FIG. 4: 2-a) and lung carcinoma cells (FIG. 4: 2-b) ) Both had no growth inhibitory effect. In addition, O naphthyl which does not have a hydroxyl group
96-hour exposure to β-D-xylopyranoside also grows on lung fibroblasts (FIG. 5: 2-c), lung carcinoma cells (FIG. 5: 2-d) and other cells (not shown) Had no effect. Also, known naphthylthioxylopyranoside (not shown) and Op-nitrophenyl-β-D-xylopyranoside did not inhibit the growth at all within the same concentration range (FIG. 6: 2-e and 2). -
f).

Test Example 2 Heparan Sulfate Elongation Activity by Xylopyranoside Compound Various cells used in Test Example 1 were used in a labeling medium (MgSO 4).
₄ was replaced with a medium containing low sulfuric acid in which MgCl ₂ was replaced).
After pre-culture, the medium was replaced with a fresh medium containing 50 μCi / ml [ ³⁵ S] sulfuric acid and various concentrations of xyloside compound. After culturing for 5 to 24 hours, the culture solution is collected and DEAE
[ ^35]
[S] was separated. Further, free glycosaminoglycan and proteoglycan were separated by octyl-sepharose hydrophobic binding chromatography.

Glycosaminoglycans and proteoglycans extended from xyloside bound to the cell surface were prepared by adding a heparin-containing phosphate buffer (100 μg heparin / ml) to 1 cm ^2.
It was liberated by treatment with 0.2 ml per unit. The substance remaining in the cells was extracted with 4M guanidine hydrochloride and 2% Triton X-100. Glycosaminoglycans and proteoglycan chains are obtained from chondroitinase ABC (manufactured by Seikagaku Corporation).
Guanidine hydrochloride / 50 mM sodium acetate: NaOAc before and after degradation of chondroitin sulfate / dermatan sulfate chain
(PH5.8) / Superose 6HR 10 / 0.2% in Triton-X-100
Chromatography by 30 was performed. Degradation by chondroitinase ABC was performed using 0.1 M Tris-HCl / 10 mM EDTA (p
Using H5.8) as a buffer, the enzyme was allowed to act overnight at 37 ° C. using 3 mU of enzyme per ml.

Normal human lung fibroblasts are expressed as O (6-hydroxy-2-naphthyl) -β-D-xylopyranoside (D-Xyl-
Glycosaminoglycan chains elongated by Nap (6) OH) and secreted into the culture medium were analyzed by Superose 6HR 10/30 chromatography to obtain a polymer (peak I), intermediate size (peak I)
I) and normal size (peak III) (FIG. 7: solid line). The normal size glycosaminoglycan of peak III is degraded by chondroitinase ABC digestion, indicating that it is chondroitin sulfate or dermatan sulfate. In contrast, most of peaks I and II are resistant to chondroitinase ABC digestion and are heparan sulfate chains because they are degraded by heparitinase (FIG. 7: dashed line).

O which is a stereoisomer of D-Xyl-Nap (6) OH
(6-Hydroxy-2-naphthyl) -β-L-xylopyranoside (L-Xyl-Nap (6) OH) had no glycosaminoglycan elongation activity in any of the cells examined. Further, O 2-naphthyl-β-D- having no hydroxyl group
Xylopyranoside (Xyl-Nap) extends not only chondroitin sulfate / dermatan sulfate chains but also heparan sulfate chains in CHO cells (Chinese hamster oocytes) (Fritz, TA et al., J. Biol. Chem. 269). , 30
0-307, 1994), nevertheless, for human lung fibroblasts and other normal and cancerous cells examined in this study, heparan sulfate has an effect of elongating chondroitin sulfate / dermatan sulfate chains. Almost no chain elongation effect was observed. Op-nitrophenyl-β-D-xylopyranoside (Xyl-PheNO ₂ ) also showed only a chondroitin sulfate / dermatan sulfate chain elongation action, as is usually said.

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 In FIG. 1, 1-a shows the effect of D-Xyl-Nap (6) OH on proliferation in human lung fibroblasts, and 1-b shows the result in human lung carcinoma cells. It is. In the figure, the vertical axis represents the cell growth rate (%), and the horizontal axis represents D-Xyl-Na
Indicates p (6) OH concentration (mM).

In FIG. 2, 1-c shows the effect of D-Xyl-Nap (6) OH on the growth of mouse 3T3 fibroblasts, and 1-d shows the effect of SV-
Investigation was performed on mouse 3T3 cells transformed at 40. In the figure, the vertical axis represents the cell growth rate (%), and the horizontal axis represents D-Xyl-Na
Indicates p (6) OH concentration (mM).

In FIG. 3, 1-e shows the effect of D-Xyl-Nap (6) OH on the growth of human umbilical vein endothelial cells, and 1-f shows the effect of human umbilical vein transformed endothelial cells. . In the figure, the vertical axis represents the cell proliferation rate (%), and the horizontal axis represents the D-Xyl-Nap (6) OH concentration (m
M).

In FIG. 4, 2-a and 2-b show the effects of O (6-hydroxy-2-naphthyl) -β-L-xylopyranoside on the growth of human lung fibroblasts (a) and human lung carcinoma cells. (B) was examined. In the figure, the vertical axis represents the cell growth rate (%), and the horizontal axis represents the xylopyranoside concentration (mM).

FIG. 5 In FIG. 5, 2-c and 2-d represent O 2-naphthyl-β
The effect of -D-xylopyranoside on proliferation was examined for human lung fibroblasts (c) and human lung carcinoma cells (d). In the figure, the vertical axis represents the cell growth rate (%),
The horizontal axis represents xylopyranoside concentration (mM).

FIG. 6 In FIG. 6, 2-e and 2-f examine the effect of Op-nitrophenyl-β-D-xylopyranoside on the growth of human lung fibroblasts (e) and human lung carcinoma cells (f). It is a thing. In the figure, the vertical axis represents the cell growth rate (%)
And the abscissa represents the xylopyranoside concentration (mM).

FIG. 7 shows [ ³⁵ S] in a human lung fibroblast secretion culture obtained by treating with 0.1 mM D-Xyl-Nap (6) OH for 5 hours.
Fig. 4 is a gel filtration chromatography of labeled glycosaminoglycan by Superose 6HR. In the figure, a solid line (-) indicates a line before treatment with chondroitinase ABC and a broken line (-
•) is the [ ³⁵ S] pattern after processing. The horizontal axis represents the fraction number, and the vertical axis represents the radioactivity (dm) of [ ³⁵ S].
p × 10 ^-2 ). In the figure, Vo represents the excluded volume, and Vt represents the column volume.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yuji Kaneda 6-8-16 Sekido, Tama-shi, Tokyo No.305 Sekido Mansion 305 (72) Hisao Yamamoto 3-594-1-406 Tateno, Higashiyamato-shi, Tokyo (72) Inventor Katsumi Sakurai 2-527-6 Kurashiki, Higashiyamato-shi, Tokyo (72) Inventor Tomoko Ashikari 9-101, Ichida, Mizutake-cho, Gamagori-shi, Aichi (72) Inventor Hiroko Habuchi Yagoto, Showa-ku, Nagoya-shi, Aichi 703 Fujimi (72) Inventor Oshi Suzuki 2-167 Hongo, Meito-ku, Nagoya-shi, Aichi Prefecture Sea-I Mansion 2nd Hongo 1004 (72) Inventor Koji Kizuna 1-1404 Uedayama, Tenpaku-ku, Nagoya-shi, Aichi (72) Inventor Anders Malmstroem Sweden Lund Sorvegatan 39 Lund University (72) Inventor Gnila Westergre - Soruson Sweden Lund Soruvegatan 39 Lund University (72) inventor Lars - Eke Fransson Sweden Lund Soruvegatan 39 Lund University

Claims (3)

[Claims] 1. A hydroxynaphthyl-β-D-xylopyranoside compound represented by the following general formula (1). Embedded image (In the formula, n is an integer of 1 or more.) 2. The compound according to claim 1, wherein in the general formula (1), n is 1. 3. A compound represented by the general formula (1):
The compound according to claim 1, which is (6-hydroxy-2-naphthyl) -β-D-xylopyranoside.