Synthesis and biological activity of new cycloalkylthiophene-Schiff bases and their Cr(III) and Zn(II) complexes

Article abstract of DOI:10.1007/s00044-009-9214-8

A series of some novel Ethyl 2-((1-hydroxynaphthalen-2-yl)methyleneamino)- 5,6-dihydro-4H-cyclopenta[b]thiopehene-3-carboxylate, Ethyl 2-((1- hydroxynaphthalen- 2-yl)methyleneamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxylate, Ethyl 2-((1-hydroxynaphtalen-2-yl)methyleneamino)-5,6,7,8- tetrahydro-4H-cyclohepta [b]thiophene-3-carboxylate and their Cr(III) and Zn(II) complexes have been synthesized. All of these substances have been examined for antibacterial activity against pathogenic strains Listeria monocytogenes 4b (ATCC-19115), Staphylococcus aureus (ATCC25923), Proteus OX2 Wrah (ETS.40-A-4), Escherichia coli (ATCC-1280), Salmonella typhi H (NCTC-901.8394), Pseudomonas putida sp., Brucella abortus (A.99, UK-1995) RSKK-03026. Sh. boydii type 11 (Pasteur51.6), Sh. boydii type 16 (cHe 67.11), Sh. boydii type 6 (RSKK-96043), and antifungal activity against Candida albicans (Y-1200-NIH, Tokyo). Some of the compounds exhibited activity comparable to ampicillin ofloxacin, nystatin, kanamycin, sulphamethoxazol, amoxycillin, and chloroamphenicol. Most of the studied compounds were found effective against bacteria studied and yeast. Birkha?user Boston 2009.

Full text of DOI:10.1007/s00044-009-9214-8

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2010) 19:576–588
DOI 10.1007/s00044-009-9214-8
ORIGINAL RESEARCH
Synthesis and biological activity of new
cycloalkylthiophene-Schiff bases and their Cr(III)
and Zn(II) complexes
Aliye Altundas Æ Nur s¸ en Sarı Æ Naki Colak Æ
¨
Hatice Og u¨ tc u¨
Received: 3 February 2009 / Accepted: 15 April 2009 / Published online: 29 May 2009
Ó Birkh a¨ user Boston 2009
Abstract A series of some novel Ethyl 2-((1-hydroxynaphthalen-2-yl)methylenea-
mino)-5,6-dihydro-4H-cyclopenta[b]thiopehene-3-carboxylate, Ethyl 2-((1-hydrox-
ynaphthalen-2-yl)methyleneamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate,
Ethyl 2-((1-hydroxynaphtalen-2-yl)methyleneamino)-5,6,7,8-tetrahydro-4H-cyclohepta
[
b]thiophene-3-carboxylate and their Cr(III) and Zn(II) complexes have been syn-
thesized. All of these substances have been examined for antibacterial activity
against pathogenic strains Listeria monocytogenes 4b (ATCC-19115), Staphylo-
coccus aureus (ATCC25923), Proteus OX2 Wrah (ETS.40-A-4), Escherichia coli
(
ATCC-1280), Salmonella typhi H (NCTC-901.8394), Pseudomonas putida sp.,
Brucella abortus (A.99, UK-1995) RSKK-03026. Sh. boydii type 11 (Pasteur51.6),
Sh. boydii type 16 (cHe 67.11), Sh. boydii type 6 (RSKK-96043), and antifungal
activity against Candida albicans (Y-1200-NIH, Tokyo). Some of the compounds
exhibited activity comparable to ampicillin ofloxacin, nystatin, kanamycin, sul-
phamethoxazol, amoxycillin, and chloroamphenicol. Most of the studied com-
pounds were found effective against bacteria studied and yeast.
Keywords Sulfur ꢀ Gewald methods ꢀ Cycloalkylthiophenes ꢀ Schiff bases ꢀ
Antimicrobial activity ꢀ Drug
A. Altundas ꢀ N. Sarı (&)
Department of Chemistry, Faculty of Science and Arts, Gazi University,
06500 Teknikokullar, Ankara, Turkey
e-mail: nursens@gazi.edu.tr
N. Colak
Department of Chemistry, Faculty of Science and Arts, Hitit University,
C¸ orum, Turkey
¨
H. Og u¨ tc u¨
Refik Saydam Hygiene Center, 06100 Ankara, Turkey

Med Chem Res (2010) 19:576–588
577
Introduction
A drug containing sulfur is an antibacterial agent because it is a competitive
inhibitor of an enzyme catalyzed reaction using p-aminobenzoic acid in the
synthesis of folic acid (Bermingham and Derrick, 2002). Ligands and complexes
that include sulfur have wide applications for the synthesis of drugs (Jain and Singh,
2006; Angelici, 1990). Therefore, there is considerable interest in the synthesis and
characterization of these compounds. However, drug resistances against antibac-
terial agents may pose a problem in their use for medical purpose (Singh et al.,
2
006). The problem could be overcome by the preparation of metal complexes,
using a process of chelation with the coordination of transition metal ions. It is well
known that N and O atoms play a key role in the coordination of metals. Schiff
bases have N atoms as their basic elements. Schiff base derivatives containing donor
atom can act as good chelating agents for the transition of metal ions (Avaji et al.,
2
008). Schiff bases and their metal complexes have been widely studied due to their
import antiparasitic (Takeuchi et al., 1999), fungicidal-bactericidal (Sari et al.,
003), and anticancer (Modi et al., 1970) properties. Substituted 2-aminothiophenes
2
have had wide applications in agrochemicals (Nawwar and Shafik, 1995), dyes and
pharmacologically active compounds (Sabnis et al., 1999), etc. However, few
studies have been performed on Schiff bases and the metal complexes derived from
aminothiophenes, including cycloalcylthiophene (Mohanan et al. 2006). This study
was designed to fill in this gap. Some new cycloalcylthiophene derivatives were
investigated to determone the antibacterial properties of Schiff bases and their
complexes, including cycloalcylthiophene derivatives. Cycloalkylaminothiophene
derivatives were synthesized by using the Gewald methods (Gewald et al., 1966;
Zhikuan et al., 2003; Hallas and Choi, 1999) (Scheme 1, 1a–c). Then, three Schiff
bases (Scheme 1, 3a–c) prepared from cycloalkylaminothiophene and 2-hydroxy-1-
napthaldehyde and their Cr(III) and Zn(II) complexes were synthesized and
characterized.
CHO
OH
CO C H
2 5
2
CN
[
S]
O
+
O
NH2
+
n
C H O
EtOH, 50 C
ο
2
5
S
n
n= 1,2,3
1
a-c
2
EtOH
Reflux
CO C H
2
2
5
N
CH
S
n
HO
3a - 3c
Scheme 1 Synthesis of Schiff bases (3a–c)

578
Med Chem Res (2010) 19:576–588
Materials and methods
All chemicals investigated in the study were reagent grade and were purified when it
was necessary. All organic solvents used in this study were purified according to
standard methods. Elemental analyses were performed with a LECO-CHNS-9320
instrument. Metal contents were determined by using a Philips PU 9285 atomic
1
13
absorption instrument. H and C-n.m.r spectra were recorded with a Bruker DPX-
00 MHz and 100 MHz using TMS as an internal standard and CDCl as solvent.
3
3
Mass spectra were recorded on a Micro Mass-UK Platform II mass spectrometer at
Tubitak, Ankara, Turkey. Electronic spectra were recorded on a Unicam-UV2-100
spectrophotometer in ethanol. IR spectra were recorded on a Mattson-5000 FT-IR
instrument in KBr pellets. Melting points were determined with a Gallenkamp
melting point apparatus. The molar conductivities were measured with a Siemens
-
3
-1
WPACM 35 conductivity meter (10 mol L
measurements were performed with a Sherwood Scientific magnetic susceptibility
in DMF solution). Magnetic
balance (Model No: MK 1) at 21°C with Hg[Co(NCS) ] as a calibration.
4
Syntheses of 2-aminothiophenes: general procedure
2
-Aminothiophene-3-carboxylic acid ethyl esters (1a–c) were prepared according to
the procedure described by Gewald (Peet et al., 1986). A mixture of 5.66 g
0.05 mol), ethyl cyanoacetate, 0.05 mol of carbonyl compound (4.20 g cyclo-
pentanone, 4.91 g cyclohexanone, and 5.60 g cycloheptanone, respectively for 1a,
b, and 1c) 1.60 g, (0.05 mol) of sulfur, 4.91 g (0.05 mol) of morpholine, and 15 ml
(
1
of ethanol was mixed at room temperature. Once an exothermal reaction was
observed and the reaction temperature was increased 50°C, after 1 hour, a thick
precipitate was obtained. This mixture was poured into the water. The resulting
solid was collected and recrystallized from ethanol.
Syntheses of imine compounds: general procedure
A mixture of 2-hydroxy-1-napthaldehyde (1.72 g, 0.01 mol) and amine compound
(
2.11 g of 1a, 2.25 g of 1b, 2.39 g of 1c, 0.01 mol) in 20 ml of ethanol was refluxed
for 2 hours and then cooled at room temperature. The precipitated solid was
collected, washed with cold ethanol, and recrystallized from ethanol. All imine
compounds were prepared by using the same procedure (Scheme 1, 3a–c).
Syntheses of complexes
All complexes were prepared by following a general method: methanolic solutions
of the ligand (0.912 g of HNAP-pT, 0.947 g of HNAP-tT, 0.983 g of HNAP-hT) 2.5
-
4
1
0
0
mol in 25 ml and metal salt (0.013 g of CrCl 6H O and 0.068 g ZnCl ) 5
3 2 2
-
4
1
mol in 25 ml were mixed and refluxed for 2 hours. The reaction mixture was,
after refluxing for 2 hours, concentrated through evaporation until half of the
volume. After keeping it another 2 days, the solid complexes formed were collected
by filtration and then dried in a desiccator over CaCl2.

Med Chem Res (2010) 19:576–588
579
Detection of antimicrobial activity
The bacterial subcultures chosen were Listeria monocytogenes 4b ATCC-19115,
Staphylococcus aureus ATCC25923, Proteus OX2 Wrah (ETS.40-A-4), Esche-
richia coli ATCC-1280, Salmonella typhi H (NCTC-901.8394), Pseudomonas
putida sp., Brucella abortus (A.99, UK-1995) RSKK-03026. Sh. boydii type 11
(
Pasteur 51.6), Sh. boydii type 16 (cHe 67.11), Sh. boydii type 6 (RSKK-96043). An
antifungal susceptibility test was used by Candida albicans Y-1200-NIH, Tokyo.
The ligands and the complexes were tested for their antimicrobial activity by the
well-diffusion method (Arslan et al., 2006; Logoglu et al., 2006). Each ligand and
complex was kept dry at room temperature and dissolved (0.25 lg/ll) in DMSO.
DMSO was used as solvent and also for control. It was found to have no
antimicrobial activity against any of the tested organisms. 1% (v/v) of a 24-hour
6
broth culture containing 10 CFU/ml was placed in sterile Petri dishes. Muller-
Hilton Agar (15 ml) kept at 45°C was then poured in to the Petri dishes and allowed
to solidity. Then 6-mm diameter wells were punched carefully by using a sterile
cork borer and were entirely filled with the test solutions. The plates were incubated
for 24 hours at 37°C. On completion of the incubation period, the mean value
obtained for the two holes was used to the calculate the zone of growth inhibition of
each sample. Bacterial subcultures and antifungal were tested for resistance to seven
antibiotics (produced by Oxoid Lt., Basingstoke, UK): ampicillin (preventing the
growth of gram-negative bacteria), ofloxacin (entering the bacterial cell and
inhibiting DNA-gyrase), nystatin (binding to sterols in the fungal cellular
membrane, altering the permeability and allowing leakage of the cellular contents),
kanamycin (used in molecular biology as agent to isolate bacteria), sul-
phamethoxazol (bacteriostatic antibacterial agent that interferes with folic acid
synthesis in susceptible bacteria), amoxycillin (b-lactam antibiotic used to treat
bacterial infections caused by susceptible microorganisms), chloroamphenicol
(
effective against a wide variety of microorganisms).
Results and discussion
Analytical data and some of the physical properties of the Schiff bases and their
complexes are summarized in Table 1. The complexes are only soluble in DMF and
DMSO but insoluble in other common organic solvents. Molar conductance values
-
1
2
-1
of the Cr(III) complexes were found to be ca. 60. X cm mol . This state
indicated that the 1:1 electrolytic behaviour for Cr(III) (Sari and G u¨ rkan 2004).
Zn(II) complexes were nonelectrolytic.
Â
Ã
Â
Ã
þ
ꢁ
MðNAP-TÞ Cl $ MðNAP-TÞ þ Cl M:CrðIIIÞ
2
2
Â
Ã
Â
Ã
MðNAP-TÞ2 $ MðNAP-TÞ M: ZnðIIÞ
2

580
Med Chem Res (2010) 19:576–588
Table 1 Analytical and physical data for Schiff bases derivatives and their complexes
Compound
empirical formula color, yield (%) (ohm cm mol
Formula weight m.p.(°C), leff (BM) K Elemental analysis found (Calcd) %
1 -1 -1
)
C
H
N
M
–
Cl
–
(HNAP-pT)
365
170–173, –
69.14 5.60 3.02
(69.04) (5.21) (3.84)
69.42 5.23 3.54
(69.66) (5.54) (3.69)
69.97 5.73 3.07
(70.23) (5.85) (3.56)
C
21
H
19NO
HNAP-tT)
21NO
3
S
White, 81
379
–
(
201–202, –
–
–
–
C
22
H
3
S
Yellow, 78
393
–
(
HNAP-hT)
23NO
Cr(NAP-pT)
152–154, –
–
–
C
23
H
3
S
Orange, 73
815.4
[
2
]Cl
208.0, 4.12
61
61.21 4.18 3.41 6.13
4.27
C
42
H
36
N
2
O
6
S
2
ClCr Dark violet, 29
(61.84) (4.66) (3.43) (6.37) (4.35)
62.79 4.51 3.71 5.76 3.81
(62.59) (4.98) (3.32) (6.16) (4.21)
63.29 6.31 2.87 5.49 3.56
(63.33) (5.28) (3.21) (5.97) (4.03)
[
Cr(NAP-tT) ]Cl
2
843.4
250.5, 4.27
62
C
44
H
40
N
2
O
6
S
2
ClCr Dark violet, 40
[
Cr(NAP-hT)
2
]Cl
871.4
199.2, 4.23
67
C
46
H
44
N
2
O
6
S
2
ClCr Dark violet, 23
[Zn(NAP-
811.4
194.0, D
62.48 4.17 3.23 8.02
–
pT) ]H O
2
2
C
42
H
38
N
2
O
7
S
2
Zn
Zn
White, 78
821.4
25
(62.11) (4.68) (3.45) (8.06)
63.94 4.71 3.11 7.48
(64.28) (4.88) (3.41) (7.96)
63.48 5.21 3.81 7.19
Zn(NAP-tT)
2
]
201.2, D
14
–
–
C
44
H
40
N
2
O
6
S
2
Yellow, 72
867.4
[Zn(NAP-
194.0, D
hT) ]H O
2
2
C
46
H
46
N
2
O
7
S
2
Zn
Orange, 75
21
(63.64) (5.30) (3.23) (7.54)
D diamagnetic
IR, UV-visible and NMR spectra of ligands and their complexes
Table 2 summarizes the main IR and UV-visible bands of the compounds. IR bands
-
in the 1612–1625 cm , 1697–1712 cm , 3409–3416 cm , and 2925–2912/
1
-1
-1
-
1
2
952–2956 cm
regions are characteristic of m(CH=N), m(C=O), m(OH), and
m(CH)arom, respectively. In the Schiff bases, the bands ca. 430 nm are attributed to
the azomethine chromophore p?p* transition (Basak et al., 2007). The bands at
higher energies (270–320 nm) are associated with the benzene p?p* transition
1
13
(
Silverstein et al., 1981). The H NMR and C NMR data of the Schiff bases are
presented in Table 3. In general, the duplets or triplets observed at 8.22–7.11 ppm
are assigned to aldehyde ring protons. The singlets at 9.30–9.32 ppm and 14.30–
1
protons of –CH and –CH of –CO C H group in the Schiff bases also are observed
4.83 ppm are assigned to imine and aromatic hydroxyl protons respectively. The
3
2
2 2 5
1
3
as expected. The C-NMR spectra data of the Schiff bases (Table 3) are in accord
with the proposed structures.
The IR assignments for the important bands of the complexes are given in
-
1
-1
Table 2. The bands in the 1697–1701 cm and 1611–1621 cm region may be,
respectively, ascribed to m(C=O) and m(–CH=N) vibrations (Joseph and Mehta,
2
007). A shift at m(C=O) bands is not seen in the complexes, lending further support

Med Chem Res (2010) 19:576–588
581
-1
-1
-1
Table 2 Key IR bands (cm ) and electronic spectral data (nm) (emax, mol cm L) of Schiff bases
and their metal complexes
4
Compound
m
(CH=N)
m
(C=O)
m
(M-O)/(M-N)
k
max (e 9 10 )
(
(
(
[
HNAP-pT)
HNAP-tT)
HNAP-hT)
Cr(NAP-pT)
1625, 1702
1625, 1696
1612, 1697
1618, 1701
275 (14), 327 (7.5), 446 (27)
270 (12), 325 (7.1), 436 (21)
271 (26), 322 (12), 429 (32)
275 (3.1), 325 (0.19)
2
]Cl
491/510
472/510
492/523
4
34 (0.14), 453 (0.10), 600 (0.09)
275 (3.5), 318 (0.42)
31 (0.09), 457 (0.19), 606 (0.06)
275 (3.9), 318 (0.42)
34 (0.07), 458 (0.18) 604 (0.08)
[
Cr(NAP-tT)
Cr(NAP-hT)
Zn(NAP-pT)
2
]Cl
1621, 1698
1621, 1698
4
[
2
]Cl
4
[
[
[
2
] ꢀ H
2
2
O
O
1618, 1701
1621, 1698
1620, 1706
479/514
472/516
452/518
261 (0.5), 320 (3.3), 442 (0.78)
261 (21), 318 (0.19), 452(0.09)
261 (21), 320 (0.08), 444 (0.02)
Zn(NAP-tT)
2
]
Zn(NAP-hT)
2
] ꢀ H
to the suggestion that the atoms O in the -C=O do not coordinate with the metal ion
Herrera et al., 2007) (Scheme 2). The azomethine and carbonyl bands in the IR
(
-
1
spectra of the complexes are in the 1697–1701 cm range, somewhat lower than
observed for the free ligands. These indicate that the azomethine nitrogen is
coordinated to metal ion (Sari et al., 2008; Burlov et al., 2006).
-
1
The IR spectra of the Zn(II) complexes exhibit brought bands in 3400 cm and
-
1
new band ca. 1600 cm (H–O–H bending mode), which are bonds because of
lattice water absorptions (Nakamoto, 1986). The IR spectra of all of the Cr(III)
complexes and [Zn(NAP-tT) ] complexes do not contain the m(OH) bands.
2
-
1
Furthermore, the appearance of new bands in the 508–587 and 472–493 cm
regions is due to m(M-O) and m(M-N), respectively (AbouEl-Enein et al., 2007).
Because Cr(III) complexes are paramagnetic, the H-NMR spectra could not be
1
1
obtained. H-NMR spectra of Zn(II) complexes were obtained due to the
diamagnetic. The Zn(II) complexes exhibit signals in the range of 9.44–9.53 ppm
due to –CH=N protons. These signals are observed in the higher field than ligands.
1
The signals ( H-NMR and IR spectra) of Zn(II) complexes are different from those
of the corresponding ligands, suggesting the coordination through oxygen atoms in a
phenol ring and azomethine groups. The imine proton signal showed a downfield
shift of approximately 0.25 ppm in Zn(II) complexes. The ligands showed broad
signals at 14.77–14.26 ppm but the complexes do not contain OH signals because
the ligands can coordinate Zn(II) ions with deprotonated phenolic oxygen except
[
[
Zn(NAP-tT) ] (Scheme 2). –OH signal is observed in different field than ligand for
2
Zn(NAP-tT) ], which state may coordinate Zn(II) ions with protonated phenolic
2
oxygen (Table 4). More detailed information about the structure of the ligands and
1
3
13
their Zn(II) complexes were provided by the C-NMR spectra data. C-NMR
spectra of the ligands were assigned by comparison with those of their Zn(II)
complexes. The signals of carbon atoms that neighbor to an OH group were
different. This can be attributed to the coordination of the phenolic oxygen atom

582
Med Chem Res (2010) 19:576–588

Med Chem Res (2010) 19:576–588
583
Scheme 2 The proposed
structures of the complexes (M:
Cr(III) and Zn(II), n = 1,2,3)
CO C H
2 5
2
CH
N
S
n
M
O
O
S
N
CH
n
C H O C
2
5 2
(
AbouEl-Enein et al., 2007) (Table 4). C , C and C carbon atoms in the free
1 2 11
Schiff bases were showed a significant shift after complexation. This case may be
due to the coordination of the ligand to the metal atom by the azomethine nitrogen
and phenolic oxygen.
Electronic spectra and magnetic studies
In the UV-vis. spectra of the complexes, the azomethine chromophore p?p*
transition is shifted to 429–452 nm, which indicates that the imino nitrogen is
involved in the coordination of the metal ion. The absorption frequencies ascribed to
the benzene p?p* transition are slightly changed as a result of the influence of the
benzene ring on the coordination interaction (Silverstein et al., 1981).
The magnetic moments for the Cr(III) complexes are 4.7 BM, indicating the
presence of three unpaired electrons. The electronic spectrum of the Cr(III) complex
4
4
exhibits band at 604 nm and 450 nm, which may be assigned to B ? E , and
1
g
g
4
4
B1g ? E transitions, respectively (Farkas et al., 2007; Cotton and Wilkinson,
g
1
972). The position of these bands is consistent with a distorted octahedral
geometry with D4h symmetry. Because Zn(II) has no unpaired d-electrons, no
absorption peak is observed in the visible region for these complexes. A tetrahedral
arrangement of the donor atoms around Zn(II) is the probable structure of the Zn(II)
complexes.
LC-mass spectra for complexes
The results obtained showed that the structure of complexes is the ML complexes
2
?
according to the LC-mass spectroscopy [M-C H ] 738.4 (m/z: %11.2), [M-C H ]
?
2
5
2 5
?
?
7
48.4 (m/z: %9.8), [M-C H ] 794.7 (m/z: %18.2), [M-C H ] 742.2 (m/z: %32.1),
2 5 2 5
?
?
[M-C H ] 770.1 (m/z: %7.1), [M-C H ] 798.7 (m/z: %7.1); for [Zn(NAP-
2 5 2 5
pT) ]H O, [Zn(NAP-tT) ], [Zn(NAP-hT) ]H O and [Cr(NAP-pT) ]Cl, [Cr(NAP-
2
2
2
2
2
2
tT) ]Cl, [Cr(NAP-hT) ]Cl, respectively. The major fragmentation pathways are
2
2
followed by the molecular ion of complexes (Scheme 3).

584
Med Chem Res (2010) 19:576–588

Med Chem Res (2010) 19:576–588
585
CO
2
C
2
H
5
(
a)
N
CH
M
N
CH
S
-
2 2 5
CO C H
n
O
S
n
O
M
N
O
O
S
S
CH
N
CH
CO
(II)
2 2 5
C H
2 2 5
CO C H
(
I)
CO
S
2
C
2
H
5
CO
2 2 5
C H
N
CH
N
CH
M
S
O
n
n
(
IV)
(III)
+
+
+
[
I- (CO
2
C
2
H
5
)] % m/z
11.2
9.8
[II-(a)]
446.4
442.4
474.7
450.2
464.1
478.7
% m/z
[III-MO]
365
% m/z
78
[
[
[
[
[
[
Zn(NAP-pT)
2
]
738.4
748.4
794.7
742.2
770.1
798.7
36
41
38
31
43
32
Zn(NAP-tT)
2
]
379
73
Zn(NAP-hT)
2
]
18.2
6.3
393
77
Cr(NAP-pT)
2
]
365
58
Cr(NAP-tT)
2
]
7.1
379
62
Cr(NAP-hT)
2
]
7.3
393
44
Scheme 3 Mass fragmentation of the complexes
Biological activity of ligands and their complexes
The ligands and their complexes were screened for antimicrobial activity in DMSO
solvent as a control substance. The compounds were tested with the same
concentrations in DMSO solution (0.25 lg/ll).
All synthesized compounds and antibiotics exhibited varying degrees of
inhibitory effects on the growth of different tested strains (Table 5). All of the
compounds were active against S. aureus, Sh. Boydii type 11, Sh. Boydii type 16,
and Sh. Boydii type 6. All synthesized compounds showed moderate activity against
S. typhi H, except Cr(III) and Zn(II) complexes of (HNAP-hT). (HNAP-hT) and its
complexes were inactive in L. monocytogenes 4b. As shown in Table 5, the
compound (HNAP-pT) showed a significant activity against S. aureus and C.
albicans; however, Proteus OX and Br. Abortus did not display any activity against
2
them.
The results of antifungal and antibacterial screening indicated that all of the
complexes of (HNAP-pT) showed more activity than the other complexes.
Generally, the metal complexes are more potent bactericides than the ligand,
except S. Aureus. Br. abortus is a gram-negative bacterium that causes premature
abortion of a cattle fetus. What makes this bacterium so dangerous is that it is
zoonotic, and it can be transferred from an animal to a human host and still remain

586
Med Chem Res (2010) 19:576–588

Med Chem Res (2010) 19:576–588
587
pathogenic (Halling et al., 2005). In humans this disease causes both acute and
chronic symptoms but can be treated with antibiotics.This research indicates that
(
HNAP-hT), [Cr(HNAP-hT) ]Cl, and [Zn(HNAP-hT) ]H O are active against Br.
2 2 2
abortus (Table 5). This enhancement in activity may be explained on the basis of
chelation theory (Kurtoglu et al., 2008). Chelation reduces the polarity of the metal
ion, so a complex has lipophilic character and increases the interaction between
metal ion and the lipid is favored. This leads to the breakdown of the permeability
barrier of the cell, resulting in interference with the normal cellular processes
(
Murukan and Mohanan, 2007). Chelation is not the only criterion for antibacterial
activity. Some important factors, such as the nature of the metal ion, nature of the
ligant, geometry of the complexes, hydrophilic, and lipophilicity, have influence on
antibacterial activity (Lippard and Berg, 1994). The antibacterial activity of these
compounds was compared with seven commercial antibiotics: kanamycin, sul-
phamethoxazol, ampicillin, chloroamphenicol, ciprofloxacin, amoxycillin, and
nystatin. The synthesized compounds were as effective as the antibiotics mentioned.
¨
Acknowlegments The authors thank the Gazi University Research Fund (Project number: 05/2009-20)
for financial support and Elif Lo g˘ o g˘ lu, Nazlıg u¨ l Tolu, and Ismail Kutlu for antibacterial studies.
_
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