Methyl caffeate as an α-glucosidase inhibitor from solanum torvum fruits and the activity of related compounds

Article abstract of DOI:10.1271/bbb.90789

In screening experiments for rat intestinal α-glucosidase (sucrase and maltase) inhibitors in 325 plants cultivated in Japan's southern island, of Tanegashima, marked inhibition against both sucrase and maltase was found in the extract of the fruit of Solanum torvum. Enzyme-assay guided fractionation of the extract led to the isolation of methyl caffeate (1) as a rat intestinal sucrase and maltase inhibitor. We examined 13 caffeoyl derivatives for sucrase- and maltase-inhibitory activities. The results showed that methyl caffeate (1) had a most favorable structure for both sucrase and maltase inhibition, except for a higher activity of methyl 3,4,5-trihydroxycinnamate (14) against sucrase. Its moderate inhibitory action against α-glucosidase provides a prospect for antidiabetic usage of S. torvum fruit.

Full text of DOI:10.1271/bbb.90789

Biosci. Biotechnol. Biochem., 74 (4), 741–745, 2010
Methyl Caffeate as an ꢀ-Glucosidase Inhibitor from Solanum torvum Fruits
and the Activity of Related Compounds
Keisuke TAKAHASHI,1 Yasuyuki YOSHIOKA,1 Eisuke KATO,1 Shigeki KATSUKI,2 Osamu IIDA,2
y
1;
Keizo HOSOKAWA,3 and Jun KAWABATA
1Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture,
Hokkaido University, Kita-ku, Sapporo 060-8589, Japan
2Tanegashima Division, Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation,
Nakatane-cho, Kumage-gun, Kagoshima 891-3604, Japan
3Department of Nutritional Management, Faculty of Health Sciences, Hyogo University, Kakogawa 675-0195, Japan
Received October 27, 2009; Accepted December 29, 2009; Online Publication, April 7, 2010
[doi:10.1271/bbb.90789]
In screening experiments for rat intestinal ꢀ-glucosi-
dase (sucrase and maltase) inhibitors in 325 plants
cultivated in Japan’s southern island, of Tanegashima,
marked inhibition against both sucrase and maltase was
found in the extract of the fruit of Solanum torvum.
Enzyme-assay guided fractionation of the extract led to
the isolation of methyl caffeate (1) as a rat intestinal
sucrase and maltase inhibitor. We examined 13 caffeoyl
derivatives for sucrase- and maltase-inhibitory activ-
ities. The results showed that methyl caffeate (1) had a
most favorable structure for both sucrase and maltase
inhibition, except for a higher activity of methyl 3,4,5-
trihydroxycinnamate (14) against sucrase. Its moderate
inhibitory action against ꢀ-glucosidase provides a
prospect for antidiabetic usage of S. torvum fruit.
perennial plant. There have been several reports on the
chemical constituents of this plant, which include well-
documented steroidal compounds13–15) and antiviral
activities,16) but no other biologically active compounds
from this plant have been reported to date. Hence, the
promising screening result prompted us to isolate and
elucidate the structures of active compounds in this
plant. Separation of S. torvum fruit extract using various
column chromatographic techniques lead to the isolation
of methyl caffeate (1) as one of active principles. Some
ꢀ-glucosidase inhibitors previously isolated from plants
contain the caffeoyl moiety as the part of their structure
and have been found to be important in exerting
inhibitory activity,3,7) but the contribution of an ester
part to the ꢀ-glucosidase-inhibitory activity of caffeic
esters has not been studied. Hence we also present
comparative results for ꢀ-glucosidase inhibition of
various synthetic caffeic esters and related compounds.
Key words: Solanum torvum; ꢀ-glucosidase inhibitor;
methyl caffeate; Tanegashima
Diabetes mellitus is one of the most serious chronic
diseases. It is caused by continual hyperglycemia and
develops along with increases in obesity and aging in the
general population.1) One of the therapeutic approaches
to decreasing postprandial hyperglycemia is to retard
absorption of glucose by inhibition of carbohydrate
hydrolyzing enzymes ꢀ-amylase and ꢀ-glucosidase in
the digestive organs.2) In recent years, many efforts have
been made to search for effective ꢀ-glucosidase inhib-
itors from natural sources in order to develop a
physiological functional food or to discover lead com-
pounds for medicinal usage against diabetes.3) In the
course of our search for rat intestinal ꢀ-glucosidase-
inhibiting principles from various plants, we have
isolated and identified several active compounds from
plants grown in Asian regions, including Japan,4–7)
Thailand,8,9) China,10,11) and Nepal.12) In this paper, we
present the results of a screening of plants cultivated in
Tanegashima, a southern island of Japan, for rat
intestinal ꢀ-glucosidase inhibition. In the screening
experiments for rat intestinal sucrase and/or maltase
inhibitors in 325 plants, potent sucrase and maltase
inhibiting activity was found in extract of the fruit of
Solanum torvum (Solanaceae), an edible herbaceous
Materials and Methods
Materials. Three hundred and twenty-five species of temperate
Japanese plants were cultivated and collected in an experimental field
in Tanegashima, Japan. All voucher specimens are deposited at the
Tanegashima Division, Research Center for Medicinal Plant Resour-
ces, National Institute for Biomedical Innovation, Tanegashima, Japan.
All chemicals used were of reagent grade, and were purchased from
Wako Pure Chemicals (Osaka, Japan), unless otherwise stated. All
solvents were distilled before use.
Apparatus. NMR spectra were recorded on a Bruker AMX500
instrument (1H, 500 MHz). Chemical shifts (ppm) were calculated
from the residual solvent signals of ꢁH 2.04 in acetone-d6, ꢁH 2.49 in
dimethyl sulfoxide (DMSO)-d6, ꢁH 3.30 in methanol-d4, or ꢁH 7.24 in
chloroform-d. Field desorption (FD), FD-high resolution (HR), and
electron ionization (EI) mass spectra were obtained on a JMS-SX102A
instrument (Jeol, Tokyo).
Intestinal ꢀ-glucosidase-inhibitory activity determination. Sucrase-
and maltase-inhibitory activities indicating inhibition of sucrase- and
maltase-hydrolyzing activities respectively in rat intestinal glucosidase
complexes were measured as described previously.7) Briefly, a crude
enzyme solution prepared from rat intestinal acetone powder (Sigma-
Aldrich Japan, Tokyo) was used as the small intestinal ꢀ-glucosidase.
A reaction mixture consisting of crude enzyme solution (0.05 ml of
maltase or 0.2 ml of sucrase), substrate solution (0.35 ml of 3.5 mM
y
To whom correspondence should be addressed. Tel/Fax: +81-11-706-2496; E-mail: junk@chem.agr.hokudai.ac.jp

742
K. TAKAHASHI et al.
maltose or 0.2 ml of 56 mM sucrose) in 0.1 M potassium phosphate
buffer (pH 6.3), and the test sample in 50% aqueous DMSO (0.1 ml)
was incubated for 15 min at 37 ꢀC. The reaction was stopped by adding
0.75 ml of 2 M Tris–HCl buffer (pH 7.0), and then this was passed
through a short column of basic alumina (Merck Japan, Tokyo) to
remove phenolic compounds, which might have interfered with
enzymatic glucose quantification at the following step. The amount
of liberated glucose was measured by the glucose oxidase method
using a commercial test kit (Glucose CII-test Wako, Wako, Osaka,
Japan).
(2.5 g, 25 mmol, 5 eq) was added to the mixture. The mixture was
refluxed for 6 h and cooled to room temperature, and the resulting
insoluble salt was filtered off. The filtrate was concentrated and
purified by silica gel column chromatography (hexane-ethyl acetate
(3:2)) to give 6 (76%).
Preparation of phenyl caffeate (7). To a stirred solution of malonic
acid (4.16 g, 40 mmol) in acetic anhydride (4.8 ml) was added conc.
H2SO4 (0.16 ml). After 20 min, acetone (4 ml) was added to the
solution and this was stirred for 6 h. The resulting precipitate was
collected to give Meldrum’s acid (66%). Meldrum’s acid (268 mg,
1.86 mmol) was then dissolved in toluene (10 ml), and phenol (188 mg,
2 mmol, 1.1 eq) was added. The mixture was heated to reflux for 5 h.
After cooling of the mixture to room temperature, 3,4-dihydroxyben-
zaldehyde (276 mg, 2 mmol, 1.1 eq), pyridine (0.5 ml), and piperidine
(0.05 ml) were added. The mixture was stirred further 12 h at room
temperature. After removal of the solvent, the mixture was diluted with
1 M HCl and extracted with ethyl acetate. The extract was washed with
water and dried over anhydrous sodium sulfate. After removal of the
solvent, the residue was purified by silica gel column chromatography
(hexane-ethyl acetate 3:2) to give 7 (10%).
Screening experiments. Screening experiments for rat intestinal
maltase and sucrase inhibition were carried out with extracts of 524
plant parts from 325 species. Dried plant parts were extracted with
50% aqueous methanol. The extracts were evaporated to dryness,
redissolved in 50% aqueous DMSO, and used as test samples to assess
rat intestinal ꢀ-glucosidase inhibitory activity. Extractable constituents
obtained from 100 mg of plant material dissolved in 1 ml of test
solution were used as the final concentration in the experiments.
Isolation of methyl caffeate (1) from S. torvum fruit. Dried fruits
(50 g) of S. torvum were extracted with 50% aqueous methanol. The
extracts were concentrated and charged onto a hydrophobic resin
column (Diaion HP-20, Mitsubishi chemical, Tokyo). The column was
washed with water to remove sugars that would have disturbed the
ꢀ-glucosidase-inhibitory assay and then eluted with methanol. The
methanol eluate was concentrated and partitioned between ethyl
acetate and water. The ethyl acetate fraction showed activities for both
sucrase (29%) and maltase (47%). In contrast, the water fraction
showed higher inhibitory activity against maltase (62%), whereas the
sucrase-inhibitory activity was low (13%). Hence further fractionation
was carried out to isolate sucrase and maltase inhibitors from the ethyl
acetate fraction. The ethyl acetate fraction was fractionated by silica
gel column chromatography with gradient elution by chloroform and
methanol. Sucrase inhibitory activity was eluted in chloroform-
methanol (4:1) eluate, while maltase inhibitory activity was dispersed
throughout the fractions. The chloroform-methanol (4:1) fraction was
further purified by preparative HPLC (column, Inertsil PREP-ODS,
ꢂ20 ꢁ 250 mm, GL-Science, Tokyo; mobile phase, 15–30% MeCN
in water (0–60 min), 30% MeCN in water (60–90 min); flow rate,
5.0 ml/min; detection, UV 254 nm). A peak eluted at tR ¼ 64:8 min
showing the highest sucrase and maltase inhibitory activities was
collected to give 1 (16 mg). The analytical data were closely consistent
with those of the authentic specimen. 1: FD-MS m=z: 194 (Mþ);
1H NMR (DMSO-d6) ꢁ (ppm): 3.67 (3H, s, OCH3), 6.25 (1H, d,
J ¼ 16:0 Hz, H-8), 6.74 (1H, d, J ¼ 8:2 Hz, H-5), 6.99 (1H, br d,
J ¼ 8:2 Hz, H-6), 7.04 (1H, br s, H-2), 7.47 (1H, d, J ¼ 16:0 Hz, H-7).
Preparation of (E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one (10). To
a stirred solution of 3,4-dihydroxybenzaldehyde (1.38 g, 10 mmol) in
DMF (50 ml) were added ethyldiisopropylamine (6.45 g, 50 mmol,
5 eq) and methoxymethyl chloride (1.9 ml, 25 mmol, 2.5 eq). The
mixture was stirred for 6 h at room temperature, diluted with water and
extracted with ethyl acetate. The extract was washed with water and
dried over anhydrous sodium sulfate. After removal of the solvent, the
residue was purified by silica gel column chromatography (hexane-
ethyl acetate 4:1) to give 3,4-bis(methoxymethoxy)benzladehyde (10a,
48%). The obtained 10a (1.08 g, 4.8 mmol) was dissolved in methanol
(25 ml) and acetone (1 ml), and KOH (2.8 g, 50 mmol, 10.4 eq) in water
(5 ml) was added to the solution. The mixture was stirred at room
temperature for 24 h. Then the mixture was poured into ice water
(50 ml), neutralized with 1 M HCl, and extracted with ethyl acetate. The
organic layer was washed with water and dried over anhydrous sodium
sulfate. After removal of the solvent, the residue was purified by silica
gel column chromatography (hexane-ethyl acetate 4:1) to give (E)-4-
[3,4-bis(methoxymethoxy)phenyl]but-3-en-2-one (10b, 42%). To a
stirred solution of 10b (50 mg, 0.19 mmol) in methanol (3 ml), 6 M HCl
(3 ml) was added dropwise. The mixture was stirred for 1 h, then
diluted with water and extracted with ethyl acetate. The organic layer
was washed with water and dried over anhydrous sodium sulfate. After
removal of the solvent, the residue was purified by silica gel column
chromatography (hexane-ethyl acetate 3:2) to give 10 (65%).
Preparation of methyl 3-(3,4-dihydroxyphenyl)propanoate (11). A
stirred solution of 1 (1.94 g, 10 mmol) in methanol (30 ml) was
hydrogenated using a balloon filled with H2 for 24 h in the presence of
10% Pd-C (106 mg). After filtering of the catalyst, the solvent was
removed and the residue was purified by silica gel column chromatog-
raphy (hexane-ethyl acetate 3:2) to give 11 (63%).
General procedure for the preparation of 2–7 and 10–14.
Compounds 2–7,17) 10,18) 11,19) and 1220) were prepared as described
below and spectral properties were matched with the reported data.
Compounds 8 and 9 are commercially available. Compounds 13 and 14
were prepared as described below.
Preparation of 2–5, and 12. To
a stirred solution of the
Preparation of methyl 2,3,4-trihydroxycinnamate (13). To a stirred
solution of 2,3,4-tris(methoxymethoxy)benzaldehyde21) (1.43 g,
corresponding cinnamic or benzoic acid (10 mmol) in each alcohol
(50 ml) was added dropwise conc. H2SO4 (2.5 ml). The reaction
mixture was heated to reflux for 6–24 h. After cooling, the resulting
mixture was concentrated, diluted with water, and extracted with ethyl
acetate. The extract was washed with water and dried over anhydrous
sodium sulfate. After removal of the solvent, the residue was purified
by silica gel column chromatography (hexane-ethyl acetate) to give the
desired esters.
5
mmol) in dioxane (10 ml) were added (methoxycarbonylmethyl)tri-
phenylphosphonium chloride (1.85 g, 5 mmol, 1 eq) in chloroform
(10 ml) and KHCO3 (2.5 g, 25 mmol, 5 eq). The mixture was refluxed
for 6 h, and cooled to room temperature, and the resulting insoluble salt
was filtered off. The filtrate was concentrated and purified by silica gel
column chromatography (hexane-ethyl acetate 4:1) to give methyl
2,3,4-tris(methoxymethoxy)cinnamate (13a, 80%). 13a: FD-HR-MS
m=z (Mþ): Calcd. for C16H22O8: 342.1315, Found: 342.1317; 1H NMR
(chloroform-d) ꢁ (ppm): 3.50 (3H, s, OCH3), 3.60 (6H, s, 2 ꢁ OCH3),
3.79 (3H, s, OCH3), 5.13, 5.18, and 5.23 (each 2H, s, 3 ꢁ OCH2), 6.38
(1H, d, J ¼ 16:1 Hz, H-8), 6.96 (1H, d, J ¼ 8:9 Hz, H-5), 7.28 (1H, d,
J ¼ 8:9 Hz, H-6), 8.02 (1H, d, J ¼ 16:1 Hz, H-7). To a stirred solution
of 13a (50 mg, 0.19 mmol) in methanol (3 ml), 6 M HCl (3 ml) was
added dropwise. The mixture was stirred for 1 h, then diluted with
water and extracted with ethyl acetate. The organic layer was washed
with water and dried over anhydrous sodium sulfate. After removal of
the solvent, the residue was purified by silica gel column chromatog-
Preparation of tert-butyl caffeate (6). To a stirred solution of
triphenylphosphine (6.0 g, 23 mmol) in toluene (20 ml) was added tert-
butyl bromoacetate (3.8 ml, 26 mmol, 1.1 eq). The reaction mixture
was heated to reflux overnight. The mixture was cooled to room
temperature and the resulting precipitate was filtered, washed
successively with toluene and hexane, and dried to give a phosphonium
salt (86%). The obtained phosphonium salt (2.35 g, 5 mmol) in
chloroform (10 ml) was added to a stirred solution of 3,4-dihydroxy-
benzaldehyde (690 mg, 5 mmol) in dioxane (10 ml) and then KHCO3

ꢀ-Glucosidase Inhibitor from Solanum torvum
743
raphy (hexane-ethyl acetate 3:2) to give 13 (35%). 13: FD-HR-MS m=z
(Mþ): Calcd. for C10H10O5: 210.0528, Found: 210.0536; 1H NMR
(DMSO-d6) ꢁ (ppm): 3.66 (3H, s, OCH3), 6.34 (1H, d, J ¼ 8:5 Hz,
H-6), 6.38 (1H, d, J ¼ 16:1 Hz, H-8), 6.93 (1H, d, J ¼ 8:5 Hz, H-5),
7.77 (1H, d, J ¼ 16:1 Hz, H-7).
Dried fruits of S. torvum were extracted with 50%
aqueous methanol. After evaporation, the crude extract
was fractionated successively by hydrophobic resin
column chromatography, solvent partition, silica gel
column chromatography, and preparative HPLC to yield
methyl caffeate (1) as an inhibitor against rat intestinal
sucrase and maltase.
Preparation of methyl 3,4,5-trihydroxycinnamate (14). Following
the method of preparing 13a, 3,4,5-tris(methoxymethoxy)benzalde-
hyde22) and (methoxycarbonylmethyl)triphenylphosphonium chloride
were reacted to give methyl 3,4,5-tris(methoxymethoxy)cinnamate
(14a) (76%). 14a: FD-HR-MS m=z (Mþ): Calcd. for C16H22O8:
342.1315, Found: 342.1308; 1H NMR (chloroform-d) ꢁ (ppm): 3.51
(6H, s, 2 ꢁ OCH3), 3.61 (3H, s, OCH3), 3.80 (3H, s, OCH3), 5.18, (2H,
s, OCH2), 5.21 (4H, s, 2 ꢁ OCH2), 6.34 (1H, d, J ¼ 15:9 Hz, H-8),
7.04 (2H, s, H-2, 6), 7.58 (1H, d, J ¼ 15:9 Hz, H-7). Following the
method of preparing 13, 14a was deprotected to give 14 (73%). 14:
FD-HR-MS m=z (Mþ): Calcd. for C10H10O5: 210.0528, Found:
210.0524; 1H NMR (DMSO-d6) ꢁ (ppm): 3.67 (3H, s, OCH3), 6.16
(1H, d, J ¼ 15:9 Hz, H-8), 6.58 (2H, s, H-2, 6), 7.38 (1H, d,
J ¼ 15:9 Hz, H-7).
Methyl caffeate (1) showed moderate inhibitory
activity, with IC50 values of 1.5 mM and 2.0 mM, against
rat intestinal sucrase and maltase respectively. These
activities are comparable to or stronger than those of
ordinary flavonoid inhibitors.23) A number of caffeoyl
esters have been isolated from plants as ꢀ-glucosidase
inhibitors.3,7,24) Although caffeic acid is assumed to be
the critical component in ꢀ-glucosidase inhibition, an
ester moiety appeared to affect ꢀ-glucosidase inhibition
also. Hence, to investigate the effects of the ester moiety
together with the caffeoyl moiety against ꢀ-glucosidase
inhibition, we synthesized or purchased a series of
caffeoyl ester 2–8 and methyl caffeate analogs 9–14, and
tested for sucrase and maltase inhibitory activities. The
compounds tested included four linear alkyl caffeates
(2–4), two branched-chain alkyl caffeates (5, 6), phenyl
caffeate (7), a ketone analog (10), methyl dihydrocaf-
feate (11), and two trihydroxycinnamates (13, 14), and
chlorogenic acid (8), caffeic acid (9), and methyl
protocatechuate (12) (Fig. 1).
The results are summarized in Table 2 and Supple-
mental Figs. 1–10 (see Biosci. Biotechnol. Biochem.
Web site). In contrast to the moderate activities of
methyl caffeate (1) against sucrase and maltase, com-
pounds 2, 3, and 4, possessing longer alkyl chains than
1, showed slight decreases in sucrase inhibition. In
branched-chain esters 5 and 6, sterically hindered tert-
butyl ester 6 showed less sucrase inhibitory activity than
smaller isopropyl ester 5. In contrast, the maltase
inhibitory activity of compounds 2–6 remained un-
changed compared to that of 1. These data suggest that
a larger alkyl group in the ester moiety was unfavorable
to sucrase inhibition in caffeoyl esters regardless of
linear or branched chains, and that maltase-inhibitory
activity was not influenced by changes in the size or
shape of the alkyl group. The sucrase inhibitory activity
of phenyl ester 7 remained unchanged as compared to 1.
So the presence of an aromatic ring in the ester moiety
is probably effective for sucrase inhibition even though
it is sterically bulky. Maybe the electronic effect of the
aromatic ring affects its conjugated caffeoyl moiety or
interaction with the enzyme, but the details were not
clear. A naturally abundant caffeic ester, chlorogenic
acid (8), showed decreased inhibitory activity against
both sucrase and maltase as compared to 1. This result
also confirms the disadvantage of a sterically hindered
ester for sucrase inhibition. On the other hand, the
decreased maltase inhibitory activity of 8 might have
been due to the hydrophilicity of the quinic ester
moiety, as the steric effect does not alter maltase
inhibition, as suggested by results for compounds 2–6.
Caffeic acid (9) and (E)-4-(3,4-dihydroxyphenyl)but-3-
en-2-one (10) also showed decreases in the maltase
inhibitory activity, but the decrease in the sucrase
inhibitory activity was not very large. The presence of a
hydrophobic ester group appeared to be important to
maltase inhibition regardless of its size. These caffeoyl
Results and Discussion
In the screening experiment, 109 samples showed
more than 50% sucrase inhibitory activity and 222
samples showed more than 50% maltase inhibitory
activity out of 524 samples from 325 plant species
(Supplemental Table 1; see Biosci. Biotechnol. Bio-
chem. Web site). Among these, notable inhibitory active
species (>90%) against rat intestinal sucrase or maltase
are shown in Table 1. Of these promising species,
Solanum torvum fruit was chosen, as it had not been
studied before as to glucosidase inhibitory activity and
was available in large quantities. Also, S. torvum fruit is
edible and might easily be applied in antidiabetic
treatment. Therefore, we started an identification of the
active principles of S. torvum fruit.
Table 1. Plant Species Showing Notable Inhibitory Activity against
Rat Intestinal Sucrase or Maltase
Inhibitory activity (%)
Scientific name
Aleurites fordii
Part
Sucrase
Maltase
stem
leaf
leaf
stem
leaf
fruit
fruit
fruit
leaf
stem
leaf
leaf
leaf
leaf
stem
33
30
100
100
96
Averrhoa bilimbi
Averrhoa carambola
Camellia japonica
Cassia angustifolia
Citrus aurantium
Citrus depressa
30
55
100
92
82
100
99
100
89
Citrus hanayu
Derris elliptica
100
100
100
61
95
98
Derris elliptica
Elaeocarpus sylvestris
Eugenia uniflora
97
90
92
42
88
90
Glochidion obovatum
Hibiscus acetosella
Ipomoea batatas (hanaimo)
99
86
100
98
100
100
100
109
100
100
100
99
Ipomoea batatas (Shimon 1 gou) stem
Liquidambar styraciflua
Morinda citrifolia
Morus australis
leaf
61
99
fruit
leaf
98
95
Morus australis
branch
leaf
leaf
Pittosporum tobira
Quassia amara
Solanum torvum
100
62
fruit
leaf
100
100
36
100
92
Styrax japonica
Swietenia macrophylla
Zanthoxylum schinifolium
leaf
stem
91
100
100

744
K. TAKAHASHI et al.
O
OH
HO
HO
OMe
O
OH
O
HO
HO
X
12
OH
O
O
HO
HO
OH
HO2C
OMe
OMe
1: X=OMe
2: X=OEt
3: X=OPr
4: X=OBu
5: X=Oi-Pr
OH OH
8
13
14
O
O
6: X=Ot-Bu
7: X=OPh
9: X=OH
HO
HO
HO
HO
OMe
10: X=Me
OH
11
Fig. 1. Structures of Methyl Caffeate (1) and Related Compounds.
Table 2. Inhibitory Activity of 1–14 against Rat Intestinal Sucrase
and Maltase
ity of S. torvum. Methyl caffeate (1) and several
derivatives (2–14) were tested for ꢀ-glucosidase inhib-
itory activity, and it was determined that 1 had a
favorable structure for both sucrase and maltase inhib-
ition, except for the slightly higher activity of 14 against
sucrase. Its moderate ꢀ-glucosidase inhibitory action
provides a promising application of Solanum torvum
fruit as an antidiabetic agent.
IC50 (mM)
Compound
Sucrase
Maltase
1
2
1.5
1.8
3.1
3.2
2.0
2.7
1.3
7.6
2.9
2.7
7.5
6.5
5.1
1.0
2.0
1.9
2.2
1.8
1.9
2.2
2.1
6.3
5.2
7.2
12.2
16.9
4.9
2.8
3
4
5
Acknowledgments
6
7
8
We are grateful to Mr. Kenji Watanabe and Dr. Eri
Fukushi of the GC-MS and NMR Laboratory, Graduate
School of Agriculture, Hokkaido University, for meas-
uring mass spectra.
9
10
11
12
13
14
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