Metal-based new sulfonamides: Design, synthesis, antibacterial, antifungal, and cytotoxic properties

Article abstract of DOI:10.3109/14756366.2011.593515

Cobalt(II), copper(II), nickel(II) and zinc(II) metal complexes with 5-chlorosalicyladehyde derived Schiff base sulfonamides have been synthesized and characterized. Structure and bonding nature of all the synthesized compounds have been deduced from phys

Full text of DOI:10.3109/14756366.2011.593515

Journal of Enzyme Inhibition and Medicinal Chemistry, 2012; 27(3): 403–412
© 2012 Informa UK, Ltd.
ISSN 1475-6366 print/ISSN 1475-6374 online
DOI: 10.3109/14756366.2011.593515
REsEaRch aRtIclE
Metal-based new sulfonamides: Design, synthesis,
antibacterial, antifungal, and cytotoxic properties
Zahid H. Chohan and Hazoor A. Shad
Department of Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan
abstract
Cobalt(II), copper(II), nickel(II) and zinc(II) metal complexes with 5-chlorosalicyladehyde derived Schiff base
sulfonamides have been synthesized and characterized. Structure and bonding nature of all the synthesized
compounds have been deduced from physical, analytical, and spectral (IR, 1H NMR, 13C NMR, Mass, electronic) data.
An octahedral geometry has been proposed for all the metal complexes. The ligands and their metal complexes have
been screened for their in vitro antibacterial, antifungal, and cytotoxic properties and results are reported.
Keywords: Sulfonamides, metal(II) complexes, antibacterial, antifungal, cytotoxic
Introduction
characterized by their physical, analytical, and spectral
data. e structure of ligands, (L1) and (L2) have been
determined by X-ray diffraction method and reported
by us elsewhere15,16. An octahedral geometry has been
suggested for all the metal (II) complexes. e ligands
and metal complexes have been screened for their
in vitro antibacterial, antifungal, and cytotoxic activity
and the data reported in this paper.
Schiff bases are known for their varied chemical and
structural characteristics and wider applications as
biologically active compounds1. Metal complexes
derived from such molecules act in drug design and
models for metalloproteins2. With the increasing inci-
dences of mycosis3, much attention has been focused
on the novel methods for synthesis of more effective
antimicrobial compounds with low toxicity. A parti-
cular interest in Schiff bases containing specifically
oxygen and nitrogen donor atoms and their metal com-
plexes speedily arose due to their inhibiting properties
towards the growth of tumours4–7. e imine bond in
Schiff bases plays role in coordination with the metals
as well as acting as highly bioactive site8–14. Keeping
in view all such aspects, we report in this paper the
synthesis of three chloro-substituted salicylaldehyde
derived Schiff base sulfonamides, 4-[(E)-(5-chloro-
2-hydroxybenzylidene)amino]-benzenesulfonamide
(L1), 4-{[(E)-(5-chlor-2-hydroxyphenyl) methylidene]
amino}-N-(5-methyl-isoxazol-3-yl)benzenesulfon-
amide (L2) and 4-{2-[(5-chloro-2-hydroxybenzylidene)
amino]ethyl}-benzenesulfonamide (L3) and their tran-
sition metal [cobalt (II), copper (II), nickel (II), and
zinc (II)] complexes. ese compounds have been
Experimental
Material and methods
Reagents and solvents used were analytical grades. All
metal (II) compounds were used as their chloride salts.
Elemental analyses were carried out with a CHNS/O
1
Analyzer (Perkin Elmer USA) model. H and 13C-NMR
spectra of compounds were recorded with a Bruker
Spectrospin Avance DPX-400 using TMS as internal stan-
dard and d6-DMSO as solvent. IR of the compounds were
recorded on a SHIMADZU FTIR spectrophotometer.
e melting points were determined with a Gallenkamp
melting point apparatus. In vitro antibacterial, antifun-
gal, and cytotoxic properties were studied at HEJ research
Institute of Chemistry, International Center for Chemical
Sciences, University of Karachi, Pakistan.
Address for Correspondence: Zahid H. Chohan, Department of Chemistry, Bahauddin Zakariya University, Multan 60800, Pakistan.
E-mail: dr.zahidchohan@gmail.com (ZHC)
(Received 25 March 2011; revised 25 May 2011; accepted 26 May 2011)
403

404 Z. H. Chohan and H. A. Shad
1H, OH); 13C NMR (δ, ppm): 37.5 (CH2-aromatic), 61.3
(CH2-N), 117.4 (C3 Cl-Ph), 126.01 (C1 Cl-Ph), 128.1 (C2,
C6 N-Ph), 127.0 (C5 Cl-Ph), 127.2 (C3, C5 N-Ph), 130.7 (C6
Cl-Ph), 132.6 (C4 Cl-Ph), 136.8 (C4 N-Ph), 142.7 (C1 N-Ph),
159.2 (C2 Cl-Ph), 160.9 (C=N, azomethine); Anal. Calcd.
for C15H15ClN2O3S (338.82): C, 53.17; H, 4.46; N, 8.27;
Found: C, 53.34; H, 4.52; N, 8.11; Mass spectrum (ESI)
[M]+ = 338.08.
General procedure for the synthesis of compounds
(L1)–(L3)
4-[(E)-(5-Chloro-2-hydroxybenzylidene)amino]
benzenesulfonamide (L1)
To a stirred solution of the respective sulfanilamide
(0.689 g, 0.004 moles) in ethanol (30 mL) was added a
solution of 5-chlorosalisylaldehyde (0.63 g, 0.004 moles)
in ethanol (15 mL). e resultant mixture was refluxed
for 3 h by monitoring the formation of product through
TLC. After completion of reaction, it was cooled to room
temperature, filtered, and volume reduced to about
one-third using rotary evaporator. e solid product
thus obtained was recrystallized in hot ethanol (86%
yield, 1.069 g). e same method was applied to prepare
ligands (L2) and (L3).
General procedure for the synthesis of complexes
(1)–(12)
[Co(L1-H)2(H2O)2] (1)
To a hot magnetically stirred dioxane (15 mL) solution
of 4-[(E)-(5-chloro-2-hydroxy benzylidene)amino]ben-
zenesulfonamide (L1; 0.622 g, 0.002 moles), an aqueous
solution (15 mL) of Co(II) Cl2.6H2O (0.238 g, 0.001 moles)
was added and refluxed for 2 h. TLC was used to moni-
tor the reaction. After the completion of reaction, the
solution was filtered and reduced to half of its volume by
evaporating in rotary evaporator. e concentrated solu-
tion was left overnight at room temperature, which led to
the formation of a solid product. It was filtered, washed
with small amount of cold solution of dioxane, then with
ether, dried and recrystallized in boiling dioxane. All
other complexes (2)–(12) were prepared following the
same method using the respective metal salts as chloride
respectively with sulfonamides.
4-[(E)-(5-Chloro-2-hydroxybenzylidene)amino]
benzenesulfonamide (L1)
Bright orange crystals; Yield 86
% (1.069 g); m.p.
196–198°C; IR (KBr, cm−1): 3345 (NH2), 3318 (OH), 1602
(HC=N), 1345, 1110 (S=O), 955 (S-N), 844 (C-S), 610
(C-Cl); 1H NMR (DMSO-d6, δ, ppm): 7.2-7.5 (m, 3H,
Cl-Ph), 7.7-8.2 (m, 4H, N-Ph), 8.91 (s, 1H, azomethine),
9.2 (s, 2H, -SO2NH2), 12.42 (s, 1H, OH); 13C NMR (δ, ppm):
117.4 (C3 Cl-Ph), 119.9 (C1 Cl-Ph), 122.6 (C2, C6 N-Ph),
127.0 (C5 Cl-Ph), 128.6 (C3, C5 N-Ph), 130.7 (C6 Cl-Ph),
132.6 (C4 Cl-Ph), 138.2 (C4 N-Ph), 156.4 (C1 N-Ph), 159.2
(C2 Cl-Ph), 160.1 (C=N, azomethine); Anal. Calcd. for
C13H11ClN2O3S (310.75): C, 50.24; H, 3.57; N, 9.01; Found:
C, 50.35; H, 3.52; N, 9.11; Mass spectrum (ESI) [M]+ = 310.
[Zn (L1-H)2(H2O)2] (4)
1H NMR (DMSO-d6, δ, ppm): 7.4-7.8 (m, 6H, Cl-Ph),
8.1-8.5 (m, 8H, N-Ph), 9.2 (s, 2H, azomethine), 9.2 (s,
4H, -SO2NH2), 10.5 (s, 4H H2O); 13C NMR (δ, ppm): 117.4
(C3 Cl-Ph), 119.9 (C1 Cl-Ph), 122.6 (C2, C6 N-Ph), 127.0
(C5 Cl-Ph), 128.6 (C3, C5 N-Ph), 130.7 (C6 Cl-Ph), 132.6
(C4 Cl-Ph), 138.2 (C4 N-Ph), 158.5 (C1 N-Ph),160.5 (C2
Cl-phenyl), 161.7 (C=N, azomethine).
4-{[(E)-(5-chloro-2-hydroxyphenyl)methylidene]amino}-N-(5-
methylisoxazol-3-yl)benzene sulfonamide (L2)
Brightorangepowder;Yield85%(1.33 g);m.p. 218–220°C;
IR (KBr, cm−1): 3365 (NH), 3315 (OH), 1597 (HC=N), 1345,
1
1110 (S=O), 955 (S-N), 844 (C-S), 615 (C-Cl); H NMR
(DMSO-d6, δ, ppm): 2.31 (s, 3H, methylisoxazole), 6.8
(s, 1H, isoxazole), 7.2-7.5 (m, 3H, Cl-Ph), 7.7-8.2 (m, 4H,
N-Ph), 8.9 (s, 1H, azomethine), 8.9 (s, 1H, SO2NH-), 12.42
(s, 1H, OH); 13C NMR (δ, ppm): 12.9 (C methylisoxazole),
95.1 (C4 isoxazole), 117.4 (C3 Cl-Ph), 119.9 (C1 Cl-Ph),
122.6 (C2, C6 N-Ph), 127.0 (C5 Cl-Ph), 128.6 (C3, C5 N-Ph),
130.7 (C6 Cl-Ph), 132.6 (C4 Cl-Ph), 138.2 (C4 N-Ph), 150.0
(C3 isoxazole), 156.4 (C1 N-Ph), 159.2 (C2 Cl-Ph), 160.9
(C=N, azomethine) 169.6 (C5 isoxazole); Anal. Calcd.
for C17H14ClN3O4S (391.82): C, 52.11; H, 3.60; N, 10.72;
Found: C, 52.23; H, 3.59; N, 10.81. Mass spectrum (ESI)
[M]+ = 391.04.
[Zn (L2-H)2(H2O)2] (8)
1H NMR (DMSO-d6, δ, ppm): 2.31 (s, 6H, methylisox-
azole), 6.8 (s, 2H, isoxazole), 7.5-7.9 (m, 6H, chloro-phe-
nyl), 8.1-8.5 (m, 8H, N-Ph), 9.1 (s, 2H, azomethine), 9.2 (s,
2H, SO2NH-), 10.5 (s, 4H, H2O); 13C NMR (δ, ppm): 12.9
(C methylisoxazole), 95.1 (C4 isoxazole), 117.4 (C3 Cl-Ph),
119.9(C1 Cl-Ph), 122.6(C2, C6 N-Ph), 127.0(C5 Cl-Ph), 128.6
(C3, C5 N-Ph), 130.7 (C6 Cl-Ph), 132.6 (C4 Cl-Ph), 138.2 (C4
N-Ph), 150.0 (C3 isoxazole), 158.5 (C1 N-Ph), 160.3 (C2
Cl-Ph), 161.5 (C=N, azomethine) 169.6 (C5 isoxazole).
[Zn (L3-H)2(H2O)2] (12)
1H NMR (DMSO-d6, δ, ppm): 3.13 (t, 4H, CH2-aromatic),
3.65 (t, 4H, CH2-N), 7.5-7.9 (m, 6H, Cl-Ph), 7.8-8.3 (m, 8H,
N-Ph), 9.1 (s, 2H, azomethine), 9.3 (s, 4H, -SO2NH2), 10.5
(s, 4H, H2O); 13C NMR (δ, ppm): 37.5 (CH2-aromatic), 62.1
(CH2-N), 117.4 (C3 Cl-Ph), 126.01 (C1 Cl-Ph), 128.1 (C2,
C6 N-Ph), 127.0 (C5 Cl-Ph), 127.2 (C3, C5 N-Ph), 130.7 (C6
Cl-Ph), 132.6 (C4 Cl-Ph), 136.7 (C4 N-Ph), 143.8 (C1 N-Ph),
160.3 (C2 Cl-Ph), 161.5 (C=N, azomethine).
4-{2-[(5-Chloro-2-hydroxybenzylidene)-amino]ethyl}
benzenesulfonamide (L3)
Yellowish green powder; Yield 76 % (1.03g); m.p. 166°C;
IR (KBr, cm−1): 3345 (NH2), 3318 (OH), 1605 (HC=N), 1345,
1
1110 (S=O), 955 (S-N), 844 (C-S), 615 (C-Cl); H NMR
(DMSO-d6, δ, ppm): 3.13 (t, 2H, CH2-aromatic), 3.34 (t,
2H, CH2-N), 7.2-7.5 (m, 3H, Cl-Ph), 7.7-8.2 (m, 4H, N-Ph),
8.91 (s, 1H, azomethine), 9.2 (s, 2H, -SO2NH2), 12.42 (s,
Journal of Enzyme Inhibition and Medicinal Chemistry

Metal-based new sulfonamides 405
values) and one vial was kept as control having 2mL of
DMF only. e solvent was allowed to evaporate over-
night. After 2 days, when shrimp larvae were ready, 1mL
of seawater and 10 shrimps were added to each vial (30
shrimps/dilution) and the volume was adjusted with sea
water to 5 mL per vial. After 24 h, the number of survivors
was counted. Data were analyzed by Finney computer
Biological properties
Antibacterial activity (in vitro)
e agar-well diffusion method17,18 was adopted to deter-
mine the antibacterial activity of newly synthesized
sulfonamides (L1)–(L3) and their metal (II) complexes
(1)–(12). e wells, about 6 mm in diameter, were dug in
the prepared media at least 24 mm apart from each other
with the help of a sterile metallic borer. 2–8h old bacte-
rial inocula, containing approximately 104–106 colony-
forming units (CFU/mL), were spread on the surface of
the nutrient agar with the help of a sterile cotton swab.
e recommended concentration (50 mg/mL) of the test
sample was prepared in DMSO and introduced in the
respective wells. Other wells supplemented with DMSO
and reference antibacterial drug (imipenum) served as
negative and positive controls, respectively. e plates
were incubated at 37°C for 24 h. Antibacterial activity was
determined by measuring the diameter (mm) of zones
showing complete inhibition. e studies of alone DMSO
showed no activity against any bacterial strains.
program to determine the LD50 values20,21
.
Results and discussion
Chemistry
Schiff bases (L1)–(L3) were prepared by refluxing an
equimolar amount of 5-chloro-2-hydroxybenzaldehyde
with the respective sulfonamides, 4-aminobenzene-
sulfonamide,
4-amino-N-(5-methyl-1,2-oxazol-3-yl)
benzenesulfonamide and 4-(2-aminoethyl)-N-(5-meth-
yl-1,2-oxazol-3-yl)benzenesulfonamide in ethanol to
successfully obtain the desired new series of Schiff
base sulfonamides in good yield (78–85%; Scheme 1.
e products were obtained as solids and their purities
were checked by thin layer chromatography. e ligands
(L1)–(L3) were only soluble in Dioxane, DMF and DMSO.
e composition of the ligands was consistent with their
microanalytical data as reported in experimental.
Antifungal activity (in vitro)
Six fungal strains, T. longifusus, C. albicans, A. flavus, M.
canis, F. solani, and C. glaberata were used to study anti-
fungal activity of all the synthesized compounds accord-
ing to the literature protocol18. Sabouraud dextrose agar
(Oxoid, Hampshire, England) was seeded with 105 (cfu)
mL−1 fungal spore suspensions and transferred to petri
plates. Discs soaked in 20 ml (200 µg/mL in DMSO) of all
compounds were placed at different positions on the agar
surface. e plates were incubated at 32°C for 7 days. e
results were recorded as % of inhibition and compared
with standard drugs miconazole and amphotericin B.
e metal (II) complexes were prepared in
a
stoichiometric (metal: ligand [1:2]) molar ratio
(Scheme 2). Physical measurements and analytical data
of the metal(II) complexes (1)–(12) also agree well with
the general formula, [M(L-H)2(OH2)2] (Tables 1 and 2).
IR spectra
e important IR spectral bands of sulfonamide deriva-
tives and their metal complexes are given in experimen-
tal and in Table 2. Sulfonamides (L1)–(L3) contain various
potential donor sites; a broad band at 3315–3318 cm−1
and a sharp band at 1597–1605 cm−1 are assigned22 to
the ν(OH) and ν(C=N) modes, respectively. Two bands
appearing at 1345 and 1110 cm−1due to νasymm(SO2) and
Minimum inhibitory concentration (MIC)
Compounds containing significant antibacterial activ-
ity (over 80%) were selected for minimum inhibitory
concentration (MIC) studies. e minimum inhibitory
concentration was determined using the disc diffu-
sion technique by preparing discs containing 10, 25, 50,
and 100 μg/mL of the compounds and applying the
protocol19.
ν
symm(SO2), respectively23 are present in all sulfonamides.
Evidences of the nitrogen bonding of the azomethine
(C=N) linkage to the metal atom stems from the shift
of the ν(C=N) frequency to lower frequency by around
32–34 cm−1 (1565–1571 cm−1) in the spectra of all of its
metal complexes. e following evidences further sup-
port the mode of chelation:
Cytotoxicity (in vitro)
Brine shrimp (Artemia salina leach) eggs were hatched in
a shallow rectangular plastic dish (22 × 32 cm), filled with
artificial seawater, which was prepared with commer-
cial salt mixture and double distilled water. An unequal
partition was made in the plastic dish with the help of
a perforated device. Approximately 50 mg of eggs were
sprinkled into the large compartment, which was dark-
ened while the matter compartment was opened to ordi-
nary light. After 2 days, nauplii were collected by a pipette
from the lighted side. A sample of the test compound was
prepared by dissolving 20 mg of each compound in 2 mL
of DMF. From this stock solutions, 500, 50, and 5 µg/mL
were transferred to 9 vials (three for each dilutions were
used for each test sample and LD50 is the mean of three
i. e disappearance of ν(OH) bands at 3315–3318 cm−1
and appearance of a new band at 1395 cm−1 due to
the ν(C-O) stretching mode in the complexes reveals
the deprotonation of the hydroxyl OH groups of the
sulfonamides. It in turn, indicates that the proton of
the OH group is replaced by the metal ions on the
formation of complexes.
ii. Appearance of the new band at 526–538 and
438–442 cm−1 due to ν(M-O) and ν(M-N) stretching
modes present in the spectra of its metal complexes
and absent in the spectra of simple sulfonamides25.
© 2012 Informa UK, Ltd.

406 Z. H. Chohan and H. A. Shad
Scheme 1. Preparation of ligands (L1)–(L3).
Scheme 2. Proposed structure of the metal(II) complexes, (1)–(12).
oxygen with the metal ion. All other protons underwent
downfield shifting by 0.25–0.35 ppm due to the increased
conjugation27 and coordination with the metal atoms.
Furthermore, the number of protons calculated from the
integration curves, and those obtained from the values of
the expected CHN analyses agree well with each other.
13C NMR spectra of the sulfonamides and their dia-
magnetic zinc (II) complexes were recorded in DMSO-
d6. e 13C NMR spectral data of sulfonamides along with
the possible assignments is recorded in the experimental
part. e carbon atoms due to heteroaromatic/aromatic
groups were found as to be in their expected region26. e
conclusions drawn from these studies provide further
support to the binding mode discussed in their IR and
1H NMR spectra. Downfield shifting of the −CH=N- signal
from 160.1–160.9 ppm in the ligands to 161.5–161.7 ppm
in its metal (II) complexes revealed coordination of the
azomethine nitrogen to the metal atom. Similarly, car-
bons of N-phenyl and Cl-phenyl rings being near to the
coordination sites also showed downfield shifting by 0.9–
1.1 ppm. All other carbons underwent downfield shifting
by 0.35–11.0 ppm due to the increased conjugation and
coordination with the metal atoms27. Furthermore, the
presences of the number of carbons agree well with the
expected values.
iii. e bands in sulfonamides due to νasymm(SO2) and
symm(SO2) appearing at 1345 and 1110cm−1 remain
ν
almost unchanged upon coordination indicating
that this group is not participating in coordination/
chelation.
iv. e bands due to ν(S-N) and ν(C-S) stretching modes
present at 955 and 844 cm−1, respectively remained
unchanged, indicating no new bond formation with
the metal ions24,25
.
1H and 13C NMR spectra
1H NMR spectra of the sulfonamides and their diamag-
netic zinc (II) complexes were recorded in DMSO-d6.
e 1H NMR spectral data along with the possible assign-
ments is recorded in the experimental part. It is observed
that all the protons due to heteroaromatic/aromatic
groups were found as to be in their expected region26.
e conclusions drawn from these studies provide fur-
ther support to the binding mode discussed in their IR
spectra. e coordination of the azomethine nitrogen is
inferred by the downfield shifting of the−CH=N- proton
signal from 8.9-8.91 ppm in the ligand to 9.1-9.2 ppm
in the complexes. Hydroxyl proton at 12.42 ppm in the
spectra of Zn (II) complexes of ligands (L1)–(L3) disap-
peared indicating deprotonation and coordination of the
Journal of Enzyme Inhibition and Medicinal Chemistry

Metal-based new sulfonamides 407
per Ni(II) ion suggesting34 also an octahedral geometry
for the Ni(II) complexes. e electronic spectra of the
Zn(II) complexes exhibited only a high-intensity band at
28,939–29,128 cm−1 and are assigned35 to a ligand-metal
charge transfer.
Electronic spectra
e Co (II) complexes exhibited well-resolved, low-en-
ergy bands at 7,296–7,409 cm−1, 17,451–17,519 cm−1 and a
strong high-energy band at 20,508–20,646 cm−1 (Table 2)
which are assigned28 to the transitions T1g(F)→4T2g(F),
4
4T1g(F)→4A2g(F) and T1g(F)→4T2g(P) in an octahedral
4
geometry29. A high-intensity band at 29,321–29,373 cm−1
was assigned to the metal to ligand charge transfer. e
magnetic susceptibility measurements for the solid Co(II)
complexes are also indicative of three unpaired electrons
per Co(II) ion suggesting30 consistency with their octahe-
dral environment.
Conductance and magnetic susceptibility
measurements
e complexes (1)–(12), are showing their nonelec-
trolytic36 nature as their molar conductance values (in
DMF) fall within the range 43.2–51.6 Ω−1 cm2 mol−1. e
magnetic moment values, at room temperature, of the
complexes are given in Table 2. e measured magnetic
moment values for cobalt (II) lie in the range of 4.87 to
4.98 B.M. indicating half spin octahedral complex. For
Cu (II) complex, the observed magnetic moment values
(1.84–1.91 B.M) lie in the range expected for a d9- system,
which contain one unpaired electron with octahedral
geometry37. e measured values (3.35–3.42 B.M.) for the
nickel (II) complexes suggest38 octahedral geometry for
these complexes. e zinc (II) complexes were found to
be diamagnetic as expected.
eelectronicspectraoftheCu(II)complexes(Table2)
showedtwolow-energyweakbandsat14,984–15,158 cm−1
and 19,166–19,209 cm−1 and a strong high-energy band
at 30,357–30,387 cm−1 and may be assigned to B1g→2A1g
2
2
and B1g→2Eg transitions, respectively31. e strong high-
energy band, in turn, is assigned to metal→ligand charge
transfer. Also, the magnetic moment values for the Cu (II)
are indicative of anti-ferromagnetic spin-spin interaction
through molecular association indicative of their octahe-
dral geometry32.
e electronic spectra of the Ni(II) complexes showed
d-dbandsintheregion10,398–10,448, 15,695–15,789, and
26,457–26,538 cm−1. ese are assigned33 to the transitions
3A2g(F)→3T2g(F), A2g(F)→3T1g(F) and A2g(F)→3T2g(P),
respectively, consistent with their well-defined octahe-
dral configuration. e band at 29,878–30,956 cm−1 was
assigned to metal→ligand charge transfer. e mag-
netic measurements showed two unpaired electrons
Pharmacology
Antibacterial activity (in vitro)
3
3
All the synthesized sulfonamides were tested against
four gram-negative (E. coli, S. flexenari, P. aeruginosa,
S. typhi) and two gram-positive (S. aureus, B. subtilis)
bacterial strains (Table 3) according to literature
protocol17,18. e results were compared with those of
Table 1. Physical measurements and analytical data of the metal (II) complexes, (1)–(12).
Elemental analysis
Compd.
(1)
Formula
[Co(L1-H)2(H2O)2]
C26H24N4O8S2Cl2Co
[MW] (g/mole)
[714.46]
Yield (%)
80
MP (°C)
224–226
C
H
N
43.71 (43.78)
3.39 (3.45)
7.84 (7.79)
(2)
[Ni(L1-H)2(H2O)2]
C26H24N4O8S2Cl2Ni
[Cu(L1-H)2(H2O)2]
C26H24N4O8S2Cl2Cu
[Zn(L1-H)2(H2O)2]
C26H24N4O8S2Cl2Zn
[Co(L2-H)2(H2O)2]
C34H30N6O10S2Cl2 Co
[Ni(L2-H)2(H2O)2]
C34H30N6O10S2Cl2 Ni
[Cu(L2-H)2(H2O)2]
C34H30N6O10S2Cl2 Cu
[Zn(L2-H)2(H2O)2]
C34H30N6O10S2Cl2 Zn
[Co(L3-H)2(H2O)2]
C30H32N4O8S2Cl2 Co
[714.22]
[719.07]
[720.93]
[876.60]
[876.36]
[881.22]
[883.08]
[770.56]
[770.32]
[775.18]
[777.04]
82
85
81
81
80
82
85
82
78
80
81
230–232
202–204
241–243
232–234
226–228
248–250
245–247
202–204
218–220
212–214
226–228
43.72 (43.26)
43.43 (43.41)
43.32 (43.39)
46.58 (46.81)
46.60 (46.79)
46.34 (46.40)
46.25 (46.46)
46.76 (46.63)
46.78 (46.65)
46.48 (46.41)
46.37 (46.32)
3.39 (3.72)
3.36 (3.39)
3.36 (3.38)
3.45 (3.34)
3.45 (3.31)
3.43 (3.32)
3.42 (3.40)
4.19 (4.22)
4.19 (4.15)
4.16 (4.19)
4.15 (4.18)
7.48 (7.52)
7.79 (7.80)
7.77 (7.72)
9.59 (9.62)
9.59 (9.65)
9.54 (9.61)
9.52 (9.56)
7.27 (7.21)
7.27 (7.29)
7.23 (7.28)
7.21 (7.26)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
[Ni(L3-H)2(H2O)2]
C30H32N4O8S2Cl2 Ni
[Cu(L3-H)2(H2O)2]
C30H32N4O8S2Cl2 Cu
[Zn(L3-H)2(H2O)2]
C30H32N4O8S2Cl2 Zn
© 2012 Informa UK, Ltd.

408 Z. H. Chohan and H. A. Shad
Table 2. Conductivity, magnetic and spectral data of the metal (II) complexes (1)–(12).
WM
Selected IR ν(cm−1)
Compd.
(W−1 cm2 mol1) B.M (meff)
λ
max (cm−1)
7409;17,451; 20,589;29,321
C=N
C-O
1395
1395
1395
1395
1395
1395
1395
1395
1395
1395
1395
1395
SO2
S-N
955
955
955
955
955
955
955
955
955
955
955
955
C-S
844
844
844
844
844
844
844
844
844
844
844
844
M-N M-O
440 526
439 538
438 532
442 528
442 535
438 534
442 525
439 538
441 529
438 537
441 535
439 528
(1)
46.5
51.6
44.5
48.2
46.7
50.2
43.2
47.6
46.8
49.1
44.6
49.1
4.98
3.42
1.91
Dia
1571
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
1345, 1110
(2)
10,398; 15,709; 26,457; 29,878 1565
(3)
14,998; 19,166; 30,379
28,939
1566
1568
1569
(4)
(5)
4.89
3.37
1.86
Dia
7368; 17,519; 20,646; 29,359
(6)
10,448; 15,789; 26,498; 30,956 1570
(7)
15,158; 19,209; 30,357
29,128
1571
1568
1569
(8)
(9)
4.96
3.35
1.84
Dia
7296; 17,498; 20,508; 29,373
(10)
(11)
(12)
10,409; 15,695; 26,538; 29,996 1570
14,984; 19,184; 30,387
28,985
1566
1568
Note: Spectroscopic characterization of compounds.
Table 3. Antibacterial bioassay of ligands and metal (II) complexes.
Compound [zone of inhibition (mm)]*
Bacteria (L1)
Gram-negative
(L2)
(L3)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12) SD
(a)
(b)
(c)
(d)
18
07
15
14
14
09
13
13
19
07
15
11
19
11
18
16
16
12
16
19
14
13
17
16
22
19
23
24
17
10
17
19
16
11
18
20
21
10
16
19
24
16
22
24
19
10
17
19
21
11
18
17
20
10
20
18
26
15
24
25
30
24
26
27
Gram-positive
(e)
(f)
18
17
17
16
18
20
21
20
18
17
17
18
22
25
20
18
19
20
19
18
25
24
17
20
20
19
18
22
26
25
30
28
SDDEV
4.2
2.8
5.1
3.6
2.4
1.9
2.1
3.5
3.4
3.9
3.3
3.6
3.6
4.2
4.2 1.7
Note: (a)=E. coli (b)=S. flexenari (c) = P. aeruginosa (d) = S. typhi (e) = S. aureus (f) = B. subtilis 10<: weak; >10: moderate; >16:
Significant SD=standard drug (Imipenum); STDEV=standard deviation; *: concentration used 1mg/mL in DMSO.
the standard drug imipenum (Figure 1). Moderate to
significant activity against all gram positive and gram
negative bacterial strains was observed for all syn-
thesized ligands except the bacterial strain (b) which
showed only small biological activity. e ligands (L1)
and (L3) exhibited significant activity (>16 mm) against
bacterial strains (a), (e), and (f) whereas, the ligand (L2)
displayed the same significant activity against (e) and
(f). On the other hand, all the three ligands showed
moderate activity (>10 mm) against bacterial strains
(c) and (d). e compounds (1)–(12) exhibited overall
a significant activity (>16 mm) against bacterial strains
(a), (c), (d), (e), and (f). However, a moderate activity
(>10 mm) was observed by compound (3) against (a)
and (b). Similarly, all the compounds (1)–(12) exhibited
moderate activity (>10 mm) against the bacterial strain
(b) except the compounds (4) and (8) which showed
significant activity. Antibacterial activity is overall
enhanced after complexation of the ligands. However,
the zinc(II) complexes of all the ligands were observed
to be the most active against all species.
the delocalization of π-electrons over the entire chelate
ring and enhances the lipophilicity of the complexes40–42
which favours its permeation through lipoid layers
of fungus and bacterial membranes and retards their
activity.
Antifungal activity (in vitro)
e antifungal screening of all the compounds was car-
ried out against fungal strains T. longifusus, C. albican,
A. flavus, M. canis, F. solani, and C. glaberate accord-
ing to the literature protocol18. e results of inhibition
were compared with the standard drugs miconazole and
amphotericin B (Figure 2).
From the data (Table 4), it was observed that ligand
(L1) showed significant activity (>75%) against (a) and
(L2) against (a) and (c) fungal strains. e ligand (L1)
showed moderate activity (51–75%) against (d) and
(e), (L2) against (e) and (L3) against (c) and (d) fungal
strains. While against all other fungal strains, the ligands
were inactive or showed very weak activity (<50%).
e metal(II) complexes (1)–(12) exhibited moderate
(51–75%) to significant (above 75%) activity against vari-
ous tested fungal strains. Complex (1) exhibited signifi-
cant activity (>75%) against (e), (3) against (d), (e), and
(f), (5) against (d), (6) against (d) and (f), (8) against (a),
(10) against (e), (11) against (d) and (e) and the complex
e increased activity of the metal complexes can
be explained on the basis of chelation theory39. Polarity
of the metal ion reduces significantly by chelation,
mainly because of partial sharing of positive charge of
metal ions with the donor groups. Further, it increases
Journal of Enzyme Inhibition and Medicinal Chemistry

Metal-based new sulfonamides 409
Figure 1. Comparison of antibacterial activity of ligands (L1)–(L3) and their complexes (1)–(12).
Figure 2. Comparison of antifungal activity of ligands (L1)–(L3) and their complexes (1)–(12).
(12) against (a), (c), and (e) fungal strains. e complexes
In vitro cytotoxic bioassay
(4)–(6) exhibited moderate activity (51–75%) against
fungal strain (a) while (2) and (6)–(11) showed moderate
activity against (b). Similarly, the complexes (2)–(4), (10)
and (11) displayed moderate (51–75%) activity against
bacterial strain (c), (7), (10), and (12) against (d), (2) and
(5) against (e) and (4), (8), and (12) against (f) fungal
strain. All other complexes were inactive or showed weak
activity (<50%).
All the synthesized compounds were screened for their
cytotoxicity (brine shrimp bioassay) using the protocol
of Meyer et al20. From the data recorded in Table 5, it
is evident that three compounds, (3), (7), and (11) dis-
played potent cytotoxic activity against Artemia salina,
while the other compounds were almost inactive for this
assay.
conclusions
Minimum inhibitory concentration (MIC) for antibacterial
activity
In the present study, in vitro antibacterial, antifungal,
and cytotoxic activities of the prepared new sulfon-
amides and their metal (II) complexes were carried
out on various bacterial/fungal strains. It was revealed
that the antibacterial and antifungal activity of the
ligands increased upon coordination/chelation. The
enhancement of the activity in ligands upon chela-
tion is reorganized on the basis of their structures and
the mode of coordination/chelation. It has been sug-
gested that chelation reduces the polarity of the metal
ion43–46 on partial sharing of its positive charge with
the donor groups. The process of chelation increases
e data obtained after preliminary antibacterial screen-
ing showed that compounds (4), (8), and (12) were the
most active (above 80%) and their average inhibition
values were 22.5 (80.36%), 22.5 (80.36%), and 23.5
(83.93%), respectively. ese compounds were there-
fore, selected for minimum inhibitory concentration
(MIC) studies. e MIC of these compounds was in the
range 1.468 × 10−8 to 1.729 × 10−7 M (Table 5). e data
showed that compound (12) proved to be the most
active against bacterial strain S. typhy as compared to
(4) and (8).
© 2012 Informa UK, Ltd.

410 Z. H. Chohan and H. A. Shad
Table 4. Antifungal bioassay (concentration used 200 µg/mL) of ligands and metal (II) complexes.
Compound [zone of inhibition (mm)]
Organism
(a)
(L1)
(L2)
(L3)
(1)
38
(2)
42
(3)
25
(4)
51
(5)
67
(6)
65
(7)
00
(8)
81
(9)
39
(10)
48
(11)
31
(12) SD
83
79
00
76
00
A
B
(b)
46
00
47
33
64
48
00
31
71
62
68
61
60
59
(c)
31
76
53
00
59
52
55
48
44
00
49
42
66
51
82
C
D
E
(d)
65
00
64
00
38
89
00
87
86
71
00
48
58
84
50
(e)
58
72
34
90
68
75
00
58
39
48
00
37
82
86
88
(f)
00
24
37
39
00
85
67
00
78
00
72
00
48
46
55
F
STD.
37.9
21.3
23.5
29.9
28.8
22.6
29.4
32.1
22.6
39.3
29.4
26.5
13.7
18.2
32.3
—
Note: (a) = T. longifucus (b) = C. Albicans (c) = A. flavus (d) = M. canis (e) = F. Solani (f) = C. glaberata SD=standard drugs MIC µg/
mL; A=Miconazole (70 µg/mL:1.6822×10−-7 M/mL), B=Miconazole (110.8 µg/mL:2.6626×10−7 M/mL), C=Amphotericin B (20 µg/
mL:2.1642×10−8 M/mL), D=Miconazole (98.4 µg/mL:2.3647×10−7 M/mL), E=Miconazole (73.25 µg/mL: 1.7603×10−7 M/mL),
F=Miconazole (110.8 µg/mL: 2.66266×10−7 M/mL); STD=standard deviation.
Table 5. Brine Shrimp bioassay data of the ligands (L1)–(L3) and their complexes (1)–(12).
Gram-negative
Gram-positive
S. aureus
Compd.
(L1)
(L2)
(L3)
(1)
LD50 (M/mL)
> 2.981×10−3
> 3.126×10−3
> 3.105×10−3
> 1.489×10−3
> 1.524×10−3
0.5986×10−3
> 1.615×10−3
> 1.365×10−3
> 1.492×10−3
0.6129×10−3
> 1.532×10−3
> 1.327×10−3
> 1.467×10−3
0.6238×10−3
> 1.389×10−3
E. coli
P. aeruginosa
S. typhi
B. subtilis
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
(2)
—
—
—
—
—
(3)
—
—
—
—
—
(4)
—
4.172×10−8
2.916×10−8
1.729×10−7
4.178×10−8
(5)
—
—
—
—
—
(6)
—
—
—
—
—
(7)
—
—
—
—
—
(8)
1.479×10−7
2.034×10−8
4.102×10−8
6.219×10−8
2.145×10−8
(9)
—
—
—
—
—
(10)
(11)
(12)
—
—
—
—
—
—
—
—
—
—
5.927×10−8
2.987×10−8
1.468×10−8
1.484×10−7
6.595×10−8
Note: e compound (3) showed activity (LD50 =5.986×10−4 M/mL), compound (7) showed activity (LD50 =6.129×10−4 M/mL) and
compound (11) showed activity (LD50 =6.238×10−4 M/mL) in the present series of compounds. It was interesting to note that only copper
complexes showed potent cytotoxicity whereas the other metal complexes did not. is activity relationship may help to serve as a basis
for future direction towards the development of certain cytotoxic agents for clinical applications.
the lipophilic nature of the metal atom, which in turn
Declaration of interest
favours40,47 its permeation through the lipoid layer of
e authors report no declarations of interest.
cell membrane of the microorganism. It has also been
suggested that some functional groups such as azome-
References
thine or heteroaromatics present in these compounds
display48,49 extensive biological activities that may be
responsible for the increase of hydrophobic charac-
ter and liposolubility of the molecules. It ultimately
enhances activity of the compounds and biological
utilization ratio.
1. Yamada S. Recent aspects of the stereochemistry of schiff-base-
metal complexes, Coord Chem. Rev 1966;1(4):415–437.
2. Jeewoth T, Bhowon MG and Wah HLK. Synthesis, characterization
and antibacterial properties of Schiff bases and Schiff base metal
complexes derived from 2,3-diamino- pyridine Trans Met Chem
1999;24:445–448.
3. Ostrosky-Zeichner L, Rex JH, Pappas PG, Hamill RJ, Larsen RA,
Horowitz HW et al. Antifungal susceptibility survey of 2,000
bloodstream Candida isolates in the United States. Antimicrob
Agents Chemother 2003;47:3149–3154.
acknowledgments
4. Lv J, Liu T, Cai S, Wang X, Liu L, Wang Y. Synthesis, structure
and biological activity of cobalt(II) and copper(II) complexes of
valine-derived schiff bases. j Inorg Biochem 2006;100:1888–1896.
5. del Campo R, Criado JJ, García E, Hermosa MR, Jiménez-Sánchez
A, Manzano JL et al. iourea derivatives and their nickel(II)
and platinum(II) complexes: antifungal activity. J Inorg Biochem
2002;89:74–82.
We are indebted to HEJ research Institute of Chemistry,
University of Karachi, Pakistan, for providing help in
taking NMR, mass spectra, antibacterial and antifungal
assays. One of us (HAZ) is grateful to Higher Education
Commission (HEC), Government of Pakistan for the
award to carry out this research.
Journal of Enzyme Inhibition and Medicinal Chemistry

Metal-based new sulfonamides 411
6. Belaid S, Landreau A, Djebbar S, Benali-Baitich O, Bouet G,
Bouchara JP. Synthesis, characterization and antifungal activity of
a series of manganese(II) and copper(II) complexes with ligands
derived from reduced N,N’-O-phenylenebis(salicylideneimine). J
Inorg Biochem 2008;102:63–69.
25. NakamotoK. (1970). Infraredspectraofinorganicandcoordination
compounds. 2nd ed. New York: Wiley Interscience.
26. Simmons WW. (1978). e Sadtler handbook of proton NMR
spectra. Philadelphia: Sadtler Research Laboratories, Inc.
27. Pasto DJ. (1969). Organic structure determination. London:
Prentice Hall International.
7. Gust R, Ott I, Posselt D, Sommer K. Development of cobalt(3,4-
diarylsalen) complexes as tumor therapeutics.
2004;47:5837–5846.
J
Med Chem
28. Lever ABP. (1984). Inorganic electronic spectroscopy. Amsterdam:
Elsevier.
8. Hassan MU, Chohan ZH, Andrea S, Supuran CT. Carbonic
anhydrase inhibitors: Schiff’s bases of aromatic and heterocyclic
sulfonamides and their metal complexes. J Enz Inhib Med Chem
2004;19:263–279.
9. Chohan ZH, Shaikh AU, Naseer MM. Metal-based isatin-bearing
sulfonamides: eir synthesis, characterization and biological
properties. Appl Organomet Chem 2006;20:729–739.
29. Estes WE, Gavel DP, Hatfield WB, Hodgson DJ. Magnetic and
structural characterization of dibromo- and dichlorobis(thiazole)
copper(II). Inorg Chem 1978;17:1415–1421.
30. Carlin RL. (1965). Transition metal chemistry. 2nd ed. New York:
Marcel Decker.
31. Burns GR. Metal complexes of thiocarbohydrazide. Inorg Chem
1968;7:277–283.
10. Chohan ZH, Antibacterial copper(II) complexes of 1,1’-symmetric
ferrocene-derived Schiff-base ligands: Studies of the effect of
anions on their antibacterial properties. Appl Organomet Chem
2002;16:17–32.
32. Chohan ZH, Kausar S. Synthesis, structural and biological studies
of nickel(II), copper(II) and zinc(II) chelates with tridentate Schiff
bases having NNO and NNS donor systems. Chem Pharm Bull
1993;41:951–953.
11. Hassan MU, Chohan ZH, Supuran CT. Antibacterial Zn(II)
compounds of Schiff bases derived from some benzothiazoles.
Main Group Metal Chem 2002;25:291–305.
12. Chohan ZH, Scozzafava A, Supuran CT. Zinc complexes of
benzothiazole-derived Schiff bases with antibacterial activity. J
Enzyme Inhib Med Chem 2003;18:259–263.
33. Balhausen CJ. (1962). An introduction to ligand field. New York:
McGraw Hill.
34. Chohan ZH, Rauf A, Naseer MM, Somra MA, Supuran CT.
Antibacterial, antifungal and cytotoxic properties of some
sulfonamide-derived chromones. J Enzyme Inhib Med Chem
2006;21:173–177.
13. Chohan ZH, Scozzafava A, Supuran CT. Unsymmetrical 1,1’-
disubstituted ferrocenes: Synthesis of Co(ii), Cu(ii), Ni(ii)
and Zn(ii) chelates of ferrocenyl -1-thiadiazolo-1’-tetrazole,
-1-thiadiazolo-1’-triazole and -1-tetrazolo-1’-triazole with anti-
35. Chohan ZH, Kausar S. Biologically active complexes of nickel(II),
copper(II) and zinc(II) with Schiff-base ligand derived from
the reaction of 2-aminopyridine and pyrrol-2-carboxaldehyde–
their synthesis and characterisation. Chem Pharm Bull
1992;40:2555–2556.
36. Geary WJ. e use of conductivity measurements in organic
solvents for the characterisation of coordination compounds.
Coord Chem Rev 1971;7:81–112.
microbial properties.
261–266.
J Enzyme Inhib Med Chem 2002;17:
14. Puccetti L, Fasolis G, Vullo D, Chohan ZH, Scozzafava A, Supuran
CT. Carbonic anhydrase inhibitors. Inhibition of cytosolic/tumor-
associated carbonic anhydrase isozymes I, II, IX, and XII with
Schiff’s bases incorporating chromone and aromatic sulfonamide
moieties, and their zinc complexes. Bioorg Med Chem Lett
2005;15:3096–3101.
15. Chohan ZH, Shad HA, Tahir MN. 4-[(E)-(5-Chloro-2-hydroxy-
benzyl-idene)amino]benzene-sulfonamide. Acta Crystallogr Sect
e Struct Rep Online 2008;65:o57.
16. Chohan ZH, Shad HA, Tahir MN, Khan IU. 4-{2-[(5-Chloro-2-
hydroxy-benzyl-idene)amino]eth-yl}benzene-sulfonamide. Acta
Crystallogr Sect e Struct Rep Online 2008;64:o725.
17. Chohan ZH. Synthesis of cobalt(II) and nickel(II) complexes
of Ceclor (cefaclor) and preliminary experiments on their
antibacterial character. Chem Pharm Bull 1991;39:1578–1580.
18. Atta-ur-Rahman, Choudhary MI, omsen WJ. (2001). Bioassay
techniques for drug development. e Netherlands: Harwood
Academic Publishers.
37. Lever ABP, Lewis
J
and Nyholm RS. Square-planar
bisethylenediamine-metal complexes.
59:2552.
J Chem Soc 1963;
38. Chohan ZH, Praveen M, Ghaffar A. Synthesis, characterisation
and biological role of anions (nitrate, sulphate, oxalate and
acetate) in Co(II), Cu(II) and Ni(II) metal chelates of some Schiff-
base derived amino acids. Synth React Inorg Met-Org Chem
1998;28:1673.
39. Jain M, Singh RV. Synthesis, characterization, and biotoxicity of
N N donor sulphonamide imine silicon(IV) complexes. Bioinorg
Chem Appl 2006;13743.
40. Chohan ZH, Shaikh AU, Supuran CT. In-vitro antibacterial,
antifungal and cytotoxic activity of cobalt (II), copper (II), nickel
(II)andzinc(II)complexeswithfuranylmethyl-andthienylmethyl-
dithiolenes: [1, 3-dithiole- 2-one and 1,3-dithiole-2-thione]. J
Enzyme Inhib Med Chem 2006;21:733–740.
19. McLaughlin JL, Chang CJ, Smith DL. (1991). In: Atta-ur-Rahman,
ed. Studies in natural products chemistry, “Bentch-Top” bioassays
for the discovery of bioactive natural products: An update,
structure and chemistry (Part-B). Vol. 9. e Netherlands: Elsevier
Science Publishers B.V., 383.
20. Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, Nichols DE,
McLaughlin JL. Brine shrimp: A convenient general bioassay for
active plant constituents. Planta Med 1982;45:31–34.
41. Chohan ZH, Supuran CT, Scozzafava A. Metal binding and
antibacterial activity of ciprofloxacin complexes. J Enzyme Inhib
Med Chem 2005;20:303–307.
42. Chohan ZH, Hazoor A, Shad, and Nasim FH. Synthesis,
characterization and biological properties of sulfonamide-
derived compounds and their transitionmetal complexes. Appl
Organometal Chem 2009;23:319–328.
43. Patel MN, Patel NH, Patel KN, Dholakiya PP, Patel DH. Synthesis,
characterization, and biocidal studies of some transition metal
complexes containing bidentate monobasic hydroxyaldehydes
and a neutral bidentate Schiff base. Synth React Inorg Metal-Org
Chem 2003;33:51–62.
21. Finney DJ. (1971). Probit analysis. 3rd ed. Cambridge: Cambridge
University Press.
22. Maurya RC, Patel P. Synthesis, magnetic and special studies of
some novel metal complexes of Cu(II), Ni(II), Co(II), Zn[II),
Nd(III), (IV), and UO2(VI) with schiff bases derived from sulfa
drugs, viz., Sulfanilamide/Sulfamerazine and o-vanillin. Spectr
Lett 1999;32(2):213–236.
23. Bellamy LJ. (1971). e infrared spectra of complex molecules.
New York: John Wiley.
24. Ferrero, JR. Low-frequency vibrations of inorganic and
coordination compounds. New York: John Wiley.
44. Chohan ZH, Sherazi SKA. Synthesis and spectroscopic studies
of biologically active Co(II), Cu(II) and Ni(II) complexes
of hydrazine derived Schiff-base ligands.
1997;19:196.
J Chem Soc Pak
45. Chohan ZH, Shad HA, Youssoufi MH, Ben Hadda T. Some new
biologically active metal-based sulfonamide. Eur J Med Chem
2010;45:2893–2901.
© 2012 Informa UK, Ltd.

412 Z. H. Chohan and H. A. Shad
46. Chohan ZH, Supuran CT. Organometallic compounds with biologi-
cally active molecules: In vitro antibacterial and antifungal activity
of some 1,1’-(dicarbohydrazono)ferrocenes and their Co (II), Cu (II),
Ni (II) and Zn (II) complexes. Appl Organomet Chem 2005;19:1207.
47. Chohan ZH, Supuran CT. In-vitro antibacterial and cytotoxic
activity of cobalt (ii), copper (ii), nickel (ii) and zinc (ii) complexes
of the antibiotic drug cephalothin (Keflin). J Enzyme Inhib Med
Chem 2005;20:463–468.
isonicotinoylhydrazide Schiff’s bases and their cobalt (II), copper
(II), nickel (II) and zinc (II) complexes. J Enzyme Inhib Med Chem
2006;21:95–103.
49. Chohan ZH. Antibacterial and antifungal ferrocene incorporated
dithiothione and dithioketone compounds. Appl. Organomet.
Chem. 2006;20:112–116.
50. Chohan ZH, Shad HA. Structural elucidation and biological
significanceof2-hydroxy-1-naphthaldehydederivedsulfonamides
and their first row d-transition metal chelates. J Enzyme Inhib Med
Chem 2008;23:369–379.
48. Chohan ZH, Arif M, Shafiq Z, Yaqub M, Supuran CT.
In vitro antibacterial, antifungal & cytotoxic activity of some
Journal of Enzyme Inhibition and Medicinal Chemistry