ALP inhibitors: Vanadyl(IV) complexes of ferulic and cinnamic acid

Article abstract of DOI:10.1515/znb-2005-0312

Two new vanadyl(IV) carboxylate complexes have been obtained: Na ₂[VO(Fer)₂(CH₃OH)₂] and Na ₂[VO(Cin)₂(CH₃O)₂] and characterized by elemental analysis and UV-vis, diff

Full text of DOI:10.1515/znb-2005-0312

ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
Evelina G. Ferrer, Mar ´ı a V. Salinas, Mar ´ı a J. Correa, Fernanda Vrdoljak, and
Patricia A. M. Williams
Centro de Qu ´ı mica Inorg a´ nica (CEQUINOR), Facultad de Ciencias Exactas, Universidad Nacional
de La Plata, C.Correo 962, 1900 La Plata, Argentina
Reprint requests to Dr. Patricia A.M. Williams. Fax: 54-221-425-9485.
E-mail: williams@dalton.quimica.unlp.edu.ar
Z. Naturforsch. 60b, 305 – 311 (2005); received September 13, 2004
Two new vanadyl(IV) carboxylate complexes have been obtained: Na [VO(Fer) (CH OH) ] and
2
2
3
2
Na [VO(Cin) (CH O) ] and characterized by elemental analysis and UV-vis, diffuse reflectance and
2
2
3
2
IR and Raman spectroscopies (FerH = ferulic acid, CinH= cinnamic acid). The thermal behavior was
2
also investigated. The inhibitory effect on alkaline phosphatase activity was tested for the compounds
and ferulic and cinnamic acids as well as for the vanadyl(IV) complex of quinic acid for comparison.
The ferulic complex together with the free ligands exhibited the lowest inhibitory effect, while the
VO/quinic and VO/cinnamic complexes showed an intermediate inhibition potential.
Key words: Vanadium, Cinnamic Complexes, Ferulic Complexes, Alkaline Phosphatase Inhibitors
Introduction
Vanadium, as an early transition metal, exhibits an
extraordinarily rich chemistry. It can be readily con-
verted between oxidation states under mild condi-
tions and then spans an unsurpassed range of reac-
tions under environmental conditions including bioac-
cumulation by organisms. This process probably in-
volves interactions with biological ligands by form-
ing strong complexes with carboxylate, aryloxide and
alkoxide functionalities [1 – 3]. Its biological and phar-
macological activity is an area of increasing research
and widespread interest. Indeed, vanadium compounds
are renowned for their potent insulin action both
in vitro and in vivo [4, 5] Several vanadium com-
plexes with insulin-like properties in glucose regu-
lation and metabolism including carboxylate-derived
ligands have been reported [6, 7]. Even though only
one variable alone cannot explain the enhancement of
insulin effects exerted by vanadium compounds, the
main action seems to be the inhibition of enzymes cat-
alyzing phosphate ester displacement reactions in the
insulin signaling pathway [6 – 8]. The inhibitory effect
Fig. 1. Schematic structure of cinnamic, ferulic and the re-
of vanadyl(IV) complexes upon alkaline phosphatases lated chlorogenic acid.
(ALP) has recently been examined [9 – 12].
Ferulic and Cinnamic acids (Fig. 1) are present in of lignosulfonates, alkaline extracts of hardwoods and
Nature and have been selected as natural biological lig- a variety of grains [13]. Also this compound is struc-
ands for the vanadyl(IV) cation. Ferulic acid (FerH2) turally related to cinnamic (CinH) and caffeic acids
has been found in products of the alkaline oxidation (the latter is a chlorogenic acid component together
0
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06
E. G. Ferrer et al. · ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
with quinic acid) [1, 2]. Hydroxycinnamic acids are by flame photometry, respectively. C and H were determined
rich in phenolic antioxidants and may reduce the in- using a Carlo Erba EA 1108 equipment.
cidence of degenerative diseases, such as cardiovascu-
lar disease and cancer, whose mechanism of action is
Preparative
Synthesis of the vanadium compounds was performed
under a high-purity nitrogen atmosphere using standard
Schlenk techniques. Solvents were dried and saturated with
believed to be initiated by free radicals.
The extracts prepared from the leaves of Ce-
cropia obtusifolia (whose main constituents are caf-
feoylquinic and chlorogenic acids) have been tradition-
ally used for the treatment of diabetes. Their effect is to
lower plasma glucose concentrations in streptozotocin-
induced diabetic rats [14]. Furthermore, chlorogenic
acid is a specific inhibitor of the glucose-6-phosphate
translocase, a component of the enzyme glucose-6-
phosphatase [15]. On the other hand, the products of
dry nitrogen. VO(acac) was freshly prepared prior to its use
2
for the synthesis of the complexes [20].
2
−
Na [VO(Fer) (CH OH) ], (Fer = Fer ): Vanadyl acety-
2
2
3
2
lacetonate (1 mmol, 0.265 g) was disssolved in methanol
◦
(
10 ml) with magnetic stirring at 50 C for 1 h. The hot so-
lution was filtered and solid ferulic acid (2 mmoles, 0.388 g)
was added in small portions under continuous stirring. The
pH was adjusted at 7.0 using freshly prepared sodium
its hydrolysis, quinic and caffeic acids, are shown to methoxide. The reaction mixture was allowed to reflux at
◦
be inactive [16].
50 C for 2 h and then evaporated to dryness using a rotatory
The aim of this work is to determine the poten- evaporator. The green powder obtained was washed several
times with warm ethyl acetate in order to eliminate the ex-
tial insulin mimetic activities of ferulic and cinnamic
cess of the ligand. The purity of the solid was tested by IR
spectroscopy selecting the band at ca. 1692 cm which cor-
acids and their new vanadyl(IV) complexes by a study
of their in vitro inhibition of phosphatase alkaline en-
zyme.
−1
responds to the free carboxylic acid group. The solid was fi-
◦
nally dried in an oven at 60 C. Yield: 65%. C H O VNa
2
2
24 11
2
(
561): calcd. C 47.1, H 4.3, Na 8.2, V 9.1; found C 47.5,
Experimental Section
H 4.1, Na 7.8, V 8.8. TG/DTA: weight loss of 11.4% was
observed below 120 C; calcd. 11.6 for 2CH OH. Endother-
Materials
◦
3
◦
Reagents were of analytical grade and were used with- mic peak was observed at 107 C. Exothermic signals were
out further purification. Cinnamic and ferulic acid were observed at 210, 274, 441 and 673 C.
◦
purchased from Sigma. Methanol (Merck) and diethyl
Ferulic sodium salt: An aqueous solution of sodium hy-
ether (Merck) were dried over 4 A molecular sieves. droxide (1 mmol in 10 ml) was added to a solution of ferulic
VO(acac)2 [17] and Na [VO(Quin) SO ].4H O [18] were acid (1 mmol, 0.388 g) in methanol (20 ml) with gentle stir-
˚
4
2
4
2
prepared and purified according to literature procedures.
ring. Addition of excess acetone produced a yellow precip-
itate, which was filtered, washed with acetone and dried in
Instrumentation
air. Yield: 82%.
−
Na [VO(Cin) (CH O) ], (Cin = Cin ): A similar pro-
IR spectra of powdered samples were measured with
a Bruker IFS 66 FTIR-spectrophotometer from 4000 to
2
2
3
2
cedure was followed to prepare the complex (70% yield).
Vanadyl acetylacetonate and cinnamic acid were used. The
compound was washed several times with diethyl ether.
−1
4
00 cm
in the form of pressed KBr pellets. Dry box
was used in the case of thermally decomposed samples. Ra-
man spectra were obtained with a Spex-Ramalog double
monochromator spectrometer, using the 514.5 nm line of an
argon ion laser for excitation. The rotating disk technique
was used, in order to avoid burning of the compound by the
laser light. Electronic absorption spectra were recorded on
a Hewlett-Packard 8453 diode-array spectrophotometer, us-
ing 1 cm quartz cells. Diffuse reflectance spectra were ob-
tained with a Shimadzu UV-300 instrument, using MgO as an
internal standard. Thermogravimetric (TG) and differential
thermal analysis (DTA) were performed on a Shimadzu sys-
tem (models TG-50 and DTA-50 respectively), working in an
C H O VNa (469): calcd. C 51.2, H 4.7, Na 9.8, V 10.9;
20 20
7
2
found C 51.0, H 4.5, Na 10.3, V 11.3. TG/DTA: no weight
◦
loss was observed below 190 C. Decomposition gradually
◦
began with exothermic peaks at 195, 243, 327 and 398 C.
Cinnamic sodium salt: 10 ml of an aqueous solution of
potassium hydroxide (1 mmol, 0.056 g) was added to a solu-
tion containing cinnamic acid (1 mmol, 0.148 g) in 10 ml of
water. After stirring, the resulting solution (pH = 12) was left
to evaporate until a white precipitate occured. The solid was
isolated by filtration, washed twice with ethanol and dried in
◦
an oven at 60 C. Yield: 85%.
◦
oxygen flow (60 ml/min) and at a heating rate of 10 C/min.
Spectrophotometric titrations
Sample quantities ranged between 10 and 20 mg. Al O was
2
3
used as a DTA standard. Vanadium and sodium contents were
Compositional studies were carried out using spectropho-
determined by the tungsto-phosphovanadic method [19] and tometric titrations. Each ligand was dissolved in methanol
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E. G. Ferrer et al. · ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
307
(
final concentration: 0.01 M) and VO(acac) was added in Table 1. Electronic absorption bands: UV-vis for VO(acac)2,
2
VO(acac) : Ferulic acid (1 : 2) in methanol (pH = 7.0) and
ligand-to-metal ratios from 10 to 0.5, in an inert atmosphere
and adjusting the final pH value to 7.0 using sodium meth-
oxide.
2
Na [VO(Cin) (CH O) ] in methanol, and diffuse reflectance
of the solid complexes.
UV-visa
2
2
3
2
Diffuse reflectancea
b2 → b1
580 (12)
582 (32)
570 (48)
b2 → e
Alkaline phosphatase assays
VO(acac)2
VO / Fer
VO / Cin
a
778 (36)
790 (73)
816 (68)
590, 705
630, 840
600, 706, 830
The effect of ferulic and cinnamic acids, vanadyl(IV)
cation and the different VO/complexes on ALP activity was
determined spectrophotometrically. The reaction was started
by the addition of the substrate (p-NPP), and the generation
−1
−1
Wavelength, nm. Molar extintion coefficient, M cm in paren-
theses.
of p-nitrophenol was monitored by the absorbance changes (d , d ) term into two levels such as for α-hydroxy-
xy yz
at 405 nm. Briefly, the experimental conditions for ALP
specific activity measurement were as follows: 1 µg/ml of
bovine intestinal ALP and 5 mM of p-NPP were dissolved
in the incubation buffer (55 mM glycine + 0.55 mM MgCl2,
pH = 10.5) and held for 10 minutes. The effects of the com-
pounds were determined by addition of different concentra-
tions (1 – 100 µM) of each compound to the pre-incubated
mixture. The effect of each concentration was tested at least
in triplicate in three different experiments. The initial rate, in
carboxylic acids [22] is not observed. In the present
cases the symmetry of the complexes is not lowered to
C . The blue shifts of the absorption bands of the two
2
v
complexes compared with the spectra of VO(acac) are
2
indicative of a weaker crystal field produced by the
negative charge of the interacting carboxylate groups
of ferulic and cinnamic acid together with methanol or
methoxide groups in the coordination sphere, respec-
absence of any compound (V ), was determined as the rate tively [23].
0
◦
of p-NPP hydrolysis at 37 C and pH = 10.5. The enzymatic
In the solid state of VO(acac) the V atom is five-
coordinated [6]. This complex forms adducts upon
dissolution in organic solvents, generating octahedral
2
reaction rates inhibited by vanadium compounds, V , were
i
determined like V but in the presence of the different con-
0
centrations of each of the investigated systems. Data were ex-
pressed as mean± SEM (SEM = standard error of the mean).
Statistical differences were analyzed by Student’s t-test.
complexes [VO(acac) L]. The coordination of the sol-
2
vent methanol (Table 1) produces a shift in the b → e
2
absorption bands of VO(acac) to lower energies. In
2
Table 1 the diffuse reflectance spectra of the two com-
plexes are compared with the spectrum of VO(acac)2.
The b → b and b → e electronic bands are blue
Results and Discussion
UV-vis and diffuse reflectance spectra
2
1
2
The electronic spectrum of the system VO/Fer has shifted in the solid state for VO/Fer and VO/Cin com-
been measured using a methanolic 1/2 solution be- plexes. This behavior is typical of vanadyl(IV) com-
cause of the low solubility of the solid complex in plexes coordinated to carboxylate groups.
many solvents. The electronic absorption bands of the
UV-vis spectra of solutions of VO/Cin and VO(acac)2
in methanol are also shown in Table 1.
According to the well-known Ballhausen and Gray
scheme [21] the d-d absorption spectra of VO(IV)
complexes with square pyramidal geometry (C4v sym-
metry) present three bands corresponding to the tran-
sitions b → e, b → b , and b → a . The latter is
2
2
1
2
1
usually masked by charge-transfer bands. The splitting
of the absorption bands is indicative of the distortion
of the square pyramidal geometry [22]. The presence
of the same pattern in the absorption spectra is dis-
tinctive of the same binding modes of the ligands. A
C4v geometry can be inferred for the three complexes
shown in Table 1. Although the coordination sphere
of the VO/cinnamic complex is suggested to be com-
Fig. 2. Spectrophotometric titration of VO2 with ferulic
acid at pH 7.0 for λ = 790 nm.
+
−
−
2
posed of 2×(COO , R-O ), the splitting of the E
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E. G. Ferrer et al. · ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
I
II
IR
III
Assignments
Table 2. Assignments of some
characteristic IR and Raman
bands (cm ) of ferulic acid(I),
ferulic sodium salt(II), and
Na2[VO(Fer)2(CH3OH)2](III).
IR
Raman
1629 s
IR
Raman
−1
1
1
692 vs
624 vs
ν(C=O), carboxylic acid
ν(C=C)
1636 m
1636 m
1592 s
1512 s
1388 s
1273 m
1030 m
1636 m
1592 w
1487 w
1393 s
1279 s
−
1
541 s
1497 m
392 s
νas(COO )
1517 m
1517 mw
1271 s
νring
−
1
νs(COO )
vs: very strong, s: strong, m: medium,
w: weak.
1
1
276 m
035 s
1266 s
1021 m
ν(aryl-O)
ν(O-CH3) (Ferulic/CH3OH)
ν(V=O)
978 s
969 s
I
II
IR
III
Assignments
Table 3. Assignments of some
characteristic IR and Raman
bands (cm ) of cinnamic acid(I),
cinnamic sodium salt(II), and
Na2[VO(Cin)2(CH3O)2](III).
IR
Raman
1636 m
1496 w
IR
Raman
−1
1684 vs
ν(C=O), carboxylic acid
ν(C=C)
1629 s
1643 m
1636 m
1533 m
1500 m
1369 m
1639 s
1533 w
1510 m
1374 m
1027 m
944 s
−
1
546 m
1498 w
407 s
νas(COO )
1495 m
νring
−
1
νs(COO )
vs: very strong, s: strong, m: medium,
w: weak.
1027 s
ν(O-CH3) (methoxide)
ν(V=O)
938 m
Spectrophotometric titrations
dance with the ionic form for the carboxylate group.
Upon coordination with the metal center, the ∆ value
In order to obtain an insight into the stoichiometry
of the complexes we have performed spectrophotomet-
ric titrations in the systems VO/Fer and VO/Cin, mon-
−
1
(
ca. 204 cm ) corresponds to a unidentate coordina-
tion of the carboxylate moiety. In the Raman spec-
trum the lowering in the intensity of the antisymmet-
ric mode is in accord with the behavior expected for
these bands [25]. The strong intensity of the symmetric
mode in the IR spectrum may be due to the superposi-
tion of other modes.
itoring absorbance changes of the b → e band as a
2
function of the ligand-to-metal ratio at constant wave-
length and pH 7.0 [24]. Fig. 2 shows the data obtained
in the VO/Fer system at λ = 790 nm. Identical results
were obtained with the VO/Cin system. The forma-
tion of 2:1 (L:M) complexes allows us to confirm that
the vanadyl(IV) cation interacts in methanolic solution
with the same stoichiometry as in the solid state.
The position of the bands, related to the stretching
modes of the methoxide group of Ferulic acid (ν(O-
CH )) remains unaltered upon complexation (IR and
3
Raman spectra) indicating the lack of interaction with
the metal center. The ν (O-CH ) stretching modes cor-
responding to the methanol solvate molecules is also
expected to appear in this region. In order to provide
Infrared and Raman spectra
Na [VO(Fer) (CH OH) ]
3
2
2
3
2
In the IR and Raman spectra (Table 2) the following more experimental data for the assignments of these
−
1
changes are observed: The strong band at 1692 cm is bands, the spectra of the complex thermal decomposi-
assigned to the (C=O) stretching of the –COOH group tion products have been recorded and mutually com-
in the free ligand and disappears when the salt and the pared. The definite decrease of the ν(O-H) vibrations
−
1
complex are formed. This bands splits into two com- of coordinated methanol observed at 3426 cm in the
◦
ponents corresponding to antisymmetric and symmet- complex (Fig. 3) at 120 C, confirms the presence of
ric stretching modes. In the sodium salt the spectrum the methanol adduct. Furthermore, the ν(CH -O) band
3
−
1
−
−1
shows two new bands at 1541 cm (νas COO ) and of coordinating methanol (1030 cm ) is overlapped
−
1
−
1
392 cm (νs COO ). A similar behavior is observed by the ν(CH -O-) of the ligand [25, 28, 29]. The grad-
3
in the spectrum of the complex where the bands ap- ual vanishing of the mode in this spectral region on
−
1
◦
pear at 1592 and 1388 cm , respectively. The differ- heating indicates the loss of methanol at 120 C and
ence ∆ν = νa(COO ) – νs(COO ), is used as a crite- the start of the decomposition of the ligand at 220 C
rion to establish the coordination of the COO group and 270 C, respectively. On the other hand, the partial
to the metal [25– 27]. The ∆ value (ca. 149 cm ) ob- decrease of the 2969 and 2941 cm and 1457, 1420,
served in the sodium salt (IR spectrum) is in concor- 1385 cm band intensities confirms the contribution
−
−
◦
−
◦
−
1
−1
−
1
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E. G. Ferrer et al. · ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
309
Fig. 4. Effect of cinnamic and ferulic acids, VO/Cinnamic,
VO/Ferulic, VO/Quinic and VO(IV) on ALP activity from
bovine intestinal mucose. The initial rate was determined by
Fig. 3. Selected parts of the infrared spectra of
Na [VO(Fer) (CH OH) ] measured after heating at
different temperatures.
2
2
3
2
◦
incubation of the enzyme at 37 C for 10 min in the absence
or presence of variable concentrations of the inhibitors. Basal
of the νa/νs(CH ) and ρ(CH ) vibrations, respectively,
−1
−1
3
3
activity was 5.2 ± 0.2 nmol pNP min µg protein. The
in these absorptions (Fig. 3).
values are expressed as mean ± SEM (n = 9).
The value of ν(V=O) observed in the complex is
characteristic of oxovanadium(IV) carboxylates [27].
80,000 molecular weight enzyme from E. coli, for
which a low-resolution X-ray crystal structure is avail-
able [37]. It is a dimer containing three non-equivalent
metal-binding sites in each subunit. Two of these are
occupied by zinc ions, one with a catalytic role and the
other one with a structural function. The third metal is
a Mg(II) cation, also playing a structural role.
Na [VO(Cin) (CH O) ]
2
2
3
2
The IR and Raman spectra showed similar features
to those of ferulic acid complex (see Table 3).
The difference ∆ν values for the potassium salt
−
1
(
1
∆ν = 139 cm ) and for the complex (∆ν =
−
1
In Fig. 4 the effects of the oxovanadium(IV) com-
plexes and the free ligands on the ALP activity are
shown. In order to compare inhibition effects with
other hydroxyacids, the alkaline phosphatase activity
of the Na4[VO(Quin)2SO4]. 4H2O [18] complex was
also tested. The effect of vanadyl(IV) cation is also dis-
played. Referring to vanadyl(IV) cation as the form of
64 cm ) suggest an ionic and unidentate coordi-
nation, respectively. The presence of the methoxide
group in the coordination sphere of the vanadium cen-
ter is inferred from the appearance of a strong IR band
−
1
at 1027 cm [30] and the absence of the band re-
−
1
lated to the OH stretching in the 3500– 3300 cm
range. The lower ν(V=O) observed in the VO/Cin with
respect to the VO/Fer complexes is indicative of the
higher σ-donating power of a methoxide ligand (com-
pared with methanol), increasing the electron density
in the metal d orbitals and reducing the pπ →dπ do-
nation from oxygen to vanadium [31, 32]. When the
coordination of VO(IV) occurs with deprotonated OH
groups of sugars or polyols, this effect is stronger and
2
+
VO in the ALP assay medium is misleading since
the vanadyl cation is only a small fraction of V(IV)
species at neutral or higher pH [8]. Given the pH value
used herein (10.5) there is no doubt that the major
−
vanadium(IV) species will be [VO(OH) ] . ALP has
3
already been proved to be sensitive to vanadium(IV)
and is a good model to test the effect of new vanadium
derivatives in vitro [8]. Only quinic and VO/Cinnamic
complexes are stronger inhibitory agents than vana-
dium(IV) in the whole concentration range (p < 0.001)
and at concentrations higher than 50 µM, respectively.
−
1
ν(V=O) bands are located at ca. 920 cm [33 – 36].
Alkaline phosphatase activity
Alkaline phosphatase (E.C.3.1.3.1) is a metalloen- On the other hand, the VO/Ferulic complex and the
zyme that catalyzes the hydrolysis of phosphate mo- free ligands behaved in a different manner than the
noesters. The most widely characterized ALP is an others denoting the lack of inhibition on the ALP ac-
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E. G. Ferrer et al. · ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
tivity. This behavior has been documented for a few The results obtained with the series of carboxy-
vanadium complexes and the lack of inhibitory activity late/VO complexes suggest:
upon phosphatases is explained by compound break-
• that the complexes having a set of hard donor
−
down in solution. However, the compounds are sup- ligands like COO and O (quinate) or CH O
−
−
3
posed to be inhibitors if the effect is determined un- (from methoxide in the cinnamate complex), that
der conditions where they remain intact [38]. It has forms particularly strong complexes with the vanadyl
been demonstrated [36] that the potency of the enzy- cation [40] better adopt the transition state structure
matic inhibition of the vanadium compounds varies of ALP, being in this way stronger inhibitors than the
considerably depending on the ancillary ligands. In- other ones.
creasing the bulkiness of the ligands by introducing
sustituents significantly decreased the inhibitory effect plex may be attributed to the lability of the coordinated
on the ALP activity. Vanadium compounds having 6- methanol molecules. The complex is thermally unsta-
• that the effect observed for the VO/Ferulic com-
◦
coordinate octahedral geometry display the lower inhi- ble (methanol is lost at 103 C) denoting weak coor-
bition on ALP activity [38].
dination to the vanadyl(IV) cation. This fact suggests
The inhibitory effect of vanadium compounds on a reduction of the possibility to adopt the appropriate
the activity of the enzymes that catalyze phosphoryl transition state symmetry in the interaction with the en-
group transference can be attributed to the formation of zyme in aqueous solution.
a trigonal bipyramidal transition state analogue. These
phosphorus-mimicking vanadium compounds, with a Conclusions
structure closer to the transition state than that of the
phosphorus compounds, likely fit more tightly into the
Two new vanadyl(IV) complexes with naturally oc-
curring ligands have been prepared and characterized.
active site, causing inhibition of the enzymatic reac- Their inhibitory effect upon specific alkaline phos-
tion [37]. Although the trigonal bipyramidal coordi- phatase activity shows a different behavior probably
nation geometry is usual for vanadium(V) but not for associated with the lability of the ligands in the coordi-
nation sphere. Ferulic and cinnamic acids do not exert
inhibition on the enzyme, an effect that was previously
determined for quinic and caffeic acids upon glucose-
the vanadyl(IV) cation, it has been recently demon-
strated that this coordination structure can be attained
by VO2+ in the presence of flexible ligands such as
6-phophatase as stated in the introductory section.
proteins and enzymes [22, 39]. However, in a recent
study it has been suggested that the best bioavailability Acknowledgements
rather than the increased potency at the phosphatase
This work was supported by CONICET, CICPBA, UNLP
enzyme active sites of vanadyl(IV) complexes com- and ANPCyT (PICT 06-06148). EGF is a member of the Re-
pared with inorganic vanadium, would be the cause of search Career from CONICET. PAMW is a member of the
their higher insulin mimetic activities [7].
Research Career from CICPBA.
[
[
[
1] E. J. Baran, J. Inorg. Biochem. 80, 1 (2000).
[9] C. Slebodnick, B. J. Hamstra, V. L. Pecoraro, Struct.
Bonding 89, 51 (1997)
[10] P. A. M. Williams, D. A. Barrio, S. B. Etcheverry, J. In-
org. Biochem. 75, 99 (1999).
2] P. W. Linder, A. Voy e´ , Polyhedron 6, 53 (1987).
3] Y. Kono, S. Kashine, T. Yoneyama, Y. Sakamoto,
Y. Matsui, H. Shibata, Biosci. Biotechnol. Biochem.
6
2, 22 (1998).
4] R. Bakhtiar, E. I. Ochiai, Gen. Pharmacol. Vasc. S 32,
25 (1999).
5] B. R. Cameron, I. R. Baird, J. Inorg. Biochem. 83, 233
2001).
[11] K. H. Thompson, C. Orvig, J. Chem. Soc., Dalton
Trans. 2885 (2000).
[
[
5
[12] S. B. Etcheverry, D. A. Barrio, P. A. M. Williams, E. J.
Baran, Biol. Trace Elem. Res. 84, 227 (2001).
[13] W. Fiddler, W. E. Parker, A. E. Wasserman, R. C. Do-
err. J. Agr. Food Chem. 15, 757 (1967) and references
therein.
[14] K. L. Johnston, M. N. Clifford, L. M. Morgan, Am. J.
Clin. Nutr. 78, 728 (2003).
[15] H. Hemmerle, H. Burger, P. Below, G. Schubert,
R. Rippel. J. Med. Chem. 40, 137 (1997).
[16] P. W. Schindler, P. Below, H. Hemmerle, H. Burger,
(
[
[
6] D. C. Crans. J. Inorg Biochem. 80, 123 (2000).
7] K. G. Peters, M. G. Davis, B. W. Howard, M. Pokross,
V. Rastogi, C. Diven, K. D. Greis, E. Eby-Wilkens,
M. Maier, A. Evdokimov, S. Soper, F. Genbauffe, J.
Inorg. Biochem. 96, 321 (2003).
[
8] D. C. Crans, J. J. Smee, E. Gaidamauskas, L. Yang,
Chem. Rev.104, 849 (2004).
Unauthenticated
Download Date | 10/4/18 9:02 PM

E. G. Ferrer et al. · ALP Inhibitors: Vanadyl(IV) Complexes of Ferulic and Cinnamic Acid
311
K. H. Sreedhara Swamy, W. J. Arion, S. Efendic, A. W.
Herling, Drug Development Research 44, 34 (1998).
17] R. A. Rowe, M. M. Jones, in T. Moller (ed.): Inorg.
Synth. Vol (V), 115, Mc. Graw-Hill Company, New
York (1957).
of Organic Molecules, Academic Press Inc., Boston
(1991).
[31] S. R. Cooper, Y. B. Koh, K. N. Raymond. J. Am. Chem.
Soc. 104, 5092 (1982).
[32] T. M. Dewey, J. DuBois, K. N. Raymond, Inorg. Chem.
32, 1729 (1993).
[33] S. B. Etcheverry, P. A. M. Williams, E. J. Baran, Carbo-
hydr. Res. 302, 131 (1997).
[
[
18] Y. Allegretti, E. G. Ferrer, A. C. Gonz a´ lez Bar o´ ,
P. A. M. Williams, Polyhedron 19, 2613 (2000).
19] R. Codd, T. W. Hambley, P. A. Lay, Inorg. Chem. 34,
[
8
77 (1995).
[34] S. B. Etcheverry, P. A. M. Williams, E. J. Baran, Carbo-
hydr. Res. 329, 41 (2000).
[
[
20] M. R. Maurya, Coord. Chem. Rev. 237, 163 (2003).
21] C. J. Ballhausen, H. B. Gray, Inorg. Chem. 1, 122
[35] P. A. M. Williams, D. A. Barrio, S. B. Etcheverry, E. J.
Baran, J. Inorg. Biochem. 98, 333 (2004).
[36] D. A. Barrio, P. A. M. Williams, A. M. Cortizo, S. B.
Etcheverry. J. Biol. Inorg. Chem. 8, 459 (2003).
[37] I. Bertini, C. Luchinat, in H. Sigel (ed.): An Insight on
the Active Site of Zinc Enzymes through Metal Sub-
stitution. Metal Ions in Biological Systems. Vol. 15,
p. 101, M. Dekker, New York (1983).
(1962).
[
[
[
[
22] E. Garriba, G. Micera, A. Panzanelli, D. Sanna, Inorg.
Chem. 42, 3981 (2003).
23] J. Selbin, L. Morpurgo, J. Inorg. Nucl. Chem. 27, 673
(
1965).
24] K. A. Connors, Binding Constants, Wiley, New York
1987).
(
25] K. Nakamoto, Infrared and Raman Spectra of Inor- [38] B. I. Posner, R. Faure, J. W. Burgess, A. P. Bevan,
th
ganic and Coordination Compounds (4 ed.), John Wi-
ley, New York (1986).
D. Lachance, G. Zhang-Sun, I. G. Fantus, J. B. Ng,
D. A. Hall, B. Soo Lum, A. Shaver. J. Biol. Chem. 6,
4596 (1994).
[26] G. B. Deacon, R. J. Phillips, Coord. Chem. Rev. 33, 227
(
1980).
[39] K. Kustin, in A. S. Tracey, D. C. Crans (eds):
Perspectives in Vanadium Biochemistry. Vanadium
Compounds: Chemistry, Biochemistry and Thera-
peutic Applications. ACS Symposium Series 711,
American Chemical Society, p.170, Washington DC
(1998).
[
[
27] E. J. Baran, J. Coord. Chem. 54, 215 (2001).
28] G. G. Nunes, D. M. Reis, P. H. C. Camargo, P. B. Hitch-
cock, M. H o¨ rner, R. M. Matos, A. S. Mangrich, E. L. de
S a´ , G. Jeffery Leigh, J. F. Soares, J. Braz. Chem. Soc.
1
4, 922 (2003).
29] P. Drozdzewski, B. Pawlak, T. Glowiak, J. Mol. Struct.
54, 111 (2003).
[
[
[40] C. V. Grant, K. M. Geiser-Busch, C. R. Cornman, R. D.
Britt, Inorg. Chem. 38, 6285 (1999).
6
30] D. Lin-Vien, N. B. Colthup, W. G. Fateley, J. G. Gras-
selli, Infrared and Raman Characteristic Frequencies
Unauthenticated
Download Date | 10/4/18 9:02 PM