schiff bases as an antimicrobial agent: a reviewschiff bases derived from o phthalaldehyde (opa) and...
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Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
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Schiff bases as an antimicrobial agent: A review
Anita Rani1*, Manoj Kumar1, Rajshree Khare2 and Hardeep Singh Tuli3
1Department of Chemistry, Maharishi Markandeshwar University, Sadopur, Ambala
2Department of Chemistry, Maharishi Markandeshwar University, Mullana, Ambala
3Department of Microbiology, Kurukshetra University, Kurukshetra
*Correspondence at: [email protected]
Received: April 16, 2015; Accepted: May 23, 2015
Abstract
Schiff bases are versatile ligands and known to be synthesized from the condensation of an
amino compound with carbonyl compounds. These compounds along with their metal complexes
are considered to be an important as catalysts in various biological processes. Also Schiff base
complexes are gaining popularity among the various industries including polymers, dyes and
pharmaceutical. This review summarizes the applications of Schiff bases and their complexes as
potent antimicrobial agents.
Key words: Schiff bases, metal complexes, antimicrobial agent.
Introduction
The first preparation of imines was reported in the 19th century by Hugo Schiff [1- 3]. The
synthesis reported by Schiff involves the condensation of a carbonyl compound with an amine
under azeotropic distillation. A Schiff base is a nitrogen analog of an aldehyde or ketone in
which the C=O group is replaced by C=N-R group as shown in Scheme [1]. It is usually formed
by condensation of an aldehyde or ketone with a primary amine [2-4].
The formation of a Schiff base from an aldehydes or ketones is a reversible reaction. Schiff bases
derived from an amino and carbonyl compound are an important class of ligands that coordinate
to metal. In azomethine derivatives, the C=N linkage is essential for biological activity, several
azomethines were reported to possess remarkable antibacterial, antifungal, anticancer and
diuretic activities. Schiff bases have wide applications in food industry, dye industry, analytical
ISSN 2394-9139 (P), 2394-9147 (O) Review article
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chemistry, catalysis, fungicidal, agrochemical and biological activities. However with growing
incidences of infectious diseases, there has been increasing emphasis on the screening of new
and more effective antimicrobial drugs with low side effects. Schiff base complexes are
considered to be among the most important stereochemical models in main group and transition
metal coordination chemistry due to their preparative accessibility and structural variety. A
considerable number of Schiff base complexes have potential biological interest, being used as
more or less successful models of biological compounds. They have not only played a seminal
role in the development of modern coordination chemistry, but also considered as key points in
the development of inorganic biochemistry, catalysis and optical materials. The present review
describes the current updates in the synthesis of Schiff base compounds.
R NH2R C R
O
C N R
R
R
H2O
Scheme 1
Where R, may be an alkyl or an aryl group. Schiff bases that contain aryl substituent are
substantially more stable and more readily synthesized, while those which contain alkyl
substituents are relatively unstable. Schiff bases of aliphatic aldehydes are relatively unstable and
readily polymerizable while those of aromatic aldehydes having effective conjugation are known
to be more stable.
Areas of Applications of Schiff Bases:
Nitro and halo derivatives of Schiff bases are reported to have antimicrobial and
antitumor activities. Antimicrobial and antifungal activities of various Schiff bases have
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also been reported. Some derivative of Schiff base & Beta- Lactam acts as good
antimicrobial agents [5].
Schiff base ligand & metal complexes of sulphur & nitrogen acts as good antibacterial
agents [1, 6].
The crown ethers of shiff bases are also examined to have a very good potential to act as
anti microbial agent [7].
Some Schiff base Copper (II) complexes with phenanthroline and bipyridyl shows better
antifungal activity to control the fungal diseases in human and plants [8].
Thiazole containing Schiff’s bases and their transition metal complexes were shown to be
extensive range of biological activities.
In a similar way there are many compounds of Schiff base with transition metals that
shows a wide range of antimicrobial activity [10-12].
The order of increasing activities is ligand < MeSnL < PhSnL < BZ3SnL, the results
matched with the previously reported data for the biological activity of organotin
complexes [13].
Fakruddin & co worker synthesized Schiff base metal complexes of Cr(III), Co(II), Ni(II) and
Cu(II) derived from 2, 6-pyridine dicarboxaldehyde-Thiosemicarbazone (PDCTC) by
conventional as well as microwave methods. In conventional method the metal complexes was
prepared by the mixing of equal moles of metal salts dissolved in the methanol followed by
addition of NaOAc (metal: ligand)in 1:1ratio. The precipitated complex was, filtered washed
with ether and recrystallized with ethanol and dried under the reduced pressure over anhydrous
CaCl2 in a desiccator while in microwave method the ligand and the metal salts was mixed in
1:1 (metal: ligand) ratio in a grinder. The Schiff base and metal complexes displayed good
activity against the Gram-positive bacteria Staphylococcus aureus, the Gram-negative bacteria
Escherichia coli and the fungi Aspergillus niger & Candida albicans. The antimicrobial results
also indicated that the metal complexes displayed better antimicrobial activity as compared to the
Schiff bases ligand. Chelation tends to make the ligand act as more powerful (Fig. 1) and potent
bactericidal agent [14].
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Fig. 1 [metal complexes obtained from 2, 6-pyridine dicarboxaldehyde-Thiosemi carbazone
(PDCTC) synthesized by Fakruddin & co worker in 2014].
Similarly they Synthesis another Novel Metal Complexes with Schiff Base 2, 5-Thiophene
Dicarboxaldehyde-Thiosemi carbazone from 2,5-Thiophene dicarboxaldehyde-Thiosemi -
carbazone(TDATC) by conventional as well as microwave methods. The Schiff base and metal
complexes displayed good activity against the Gram- positive bacteria Staphylococcus aureus,
the Gram- negative bacteria, Escherichia coli and the fungi Aspergillus niger [15].
R. Selwin Joseyphus & co worker prepared Schiff base ligands metal complexes with Zn(II). The
Zn(II) complex was prepared by dissolving Zn(II) nitrate with ligand in methanol [16].The in
vitro biological screening effects of the investigated compounds were tested against the bacterial
species Staphylococcus aureus, Escherichia coli, Klebsiella pneumaniae, Proteus vulgaris and
Pseudomonas aeruginosa and fungal species Aspergillus niger, Rhizopus stolonifer, Aspergillus
flavus, Rhizoctonia bataicola and Candida albicans by the disc diffusion method (Fig.2).
N
N N
HH
NH NH
N N
H H
N
S S
M
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Fig. 2 [Schiff base metal complex formed after condensation of glycylglycine with indole-3-
carboxaldehyde. Synthesized by R. Selwin Joseyphus & co worker in 2008]
Pillutla Sambasiva et al Synthesize & characterize the antimicrobial activity of tridentate Schiff
base ligands containing pyrazolone moiety and their transition metal complexes of VO(II),
Cu(II), Fe(III), and Co(II). The metal complexes of these ligands with VO(II), Cu(II), Fe(III),
and Co(II) show varying geometries. (Fig. 3-5).The ligands and metal complexes show extensive
antibacterial and antifungal activity. In general Fe(III) and Co(II) complexes are more potent
than other complexes and ligands. The complexes show enhanced antibacterial and anti- fungal
activity against various microbscompared to the ligands[17].
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N
N
N X
OH
Fig. 3 [Schiff base ligand was prepared by reacting 3-methyl-1-phenyl-4-acetylpyrazolin -5-
ol with 1,2-diaminobenzene, and 2-aminophenol by Pillutla Sambasiva et al in 2010]
Fig. 4 [Metal complex of above Schiff base ligand prepared by Pillutla Sambasiva et al in
2010]
N
N
N
O
N H 2
V
O C H 3
H
O
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N
N
N
O
NH2
Cu
H2N N
N
N
O
Fig. 5 [Condensation of two molecules of given ligand to form a new metal complex
synthesized by Pillutla Sambasiva et al in 2010]
M. B. Fugu et al [18] prepared transition metal complexes of Mn(II), Co(II), Ni(II), Cu(II) and
Zn(II) with Schiff base ligand .The Schiff base ligand was prepared by condensation of vanillin
with 2-aminophenol in ethanol. Schiff base metal (II) complexes was prepared by adding drop
metal(II) salts [MnCl2.4H2O, CoCl2.6H2O, NiCl2.6H2O, Cu(CH3COO)2.H2O and
Zn(CH3COO)2.2H2O] in boiling ethanol( Fig. 6). The Schiff base ligands and the metal
complexes were assayed with the bacteria Escherichia coli, Salmonella typhi, Klebsiella
pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptocuccus pyogenes,
Corynebacterium specie, and Basillus subtilis using disc diffusion method. The metal complexes
were found to be more effective against these micro organisms.
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HO
N
CH
O
OH CH3
O
CH
N
OH
M
CH3
X
X
OH
Fig. 6 [Schiff base metal complex prepared by condensation of vanillin with 2-aminophenol
in ethanol with metal solution given by M. B. Fugu et al in 2013]
K. R. Joshi & co workers [19] synthesized Schiff Base Metal Complexes from 2 -Hydroxy-3-
methoxy-5-nitrobenzaldehyde & newly synthesized compound was tested for their antibacterial
activities & found to be very affective. Neelakantan et al, synthesized Metal complexes with
Schiff bases derived from o phthalaldehyde (opa) and amino acids viz., glycine (gly) l-alanine
(ala), l-phenylalanine (pal) [20]. The antimicrobial activities of the Schiff base metal complexes
were tested in vitro against eleven microbes by the modified disc diffusion method. Cu(II) and
Ni(II) complexes exhibit inhibition towards all the studied microorganisms. However, Co(II) and
Mn(II) complexes exhibit less inhibition and VO(II) complexes have no activity towards the
microorganisms. Four new N2O2 type tetradentate Schiff base complexes of Co(III), derived
from the condensation of meso-1,2 diphenyl-1,2-ethylenediamine (mesostilbenediamine) with
salicylaldehyde derivatives, were synthesized [20]. The in vitro antimicrobial activity of the
Schiff base complexes was tested against various human pathogenic bacteria [Fig.7].
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N
OH
N
O
Co
Py
Py
PF6
Fig. 7 [Schiff Base Metal Complexes derived from 2 -Hydroxy-3-methoxy-5-
nitrobenzaldehyde synthesized by K.R.Joshi and co-worker in 2007]
Pallavi Goel & co workers [21] synthesized schiff base ligand & their transition metal complex
(Mn (II),Cu (II),Co(II) & appropriate balance between broad spectrum pharmacological profile.
Tetradentate macrocyclic ligand [1,2,5,6tetraoxo-3,4,7,8 tetraaza-(1,2,3,4,5,6,7,8) tetrabenzene]
and its transition metal complex of Mn(II) [Fig. 8]. The LD50 values of the ligand and its metal
complex has been. The screened antimicrobial Activity also examined against different bacteria
and plant fungi. The result was showing that macrocyclic ligand was potentially more active
towards tested microbial species than metal complex.
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Fig. 8 (Mn(II) complex of 1,2,5,6tetraoxo-3,4,7,8tetraaza- (1,2,3,4,5,6,7,8) tetrabenzene
synthesized by Pallavi Goel & co workers in 2014).
Another example is Tetraaza macrocyclic Cu(II) complexes of composition [CuLX2] (where L =
N4 donor macrocyclic ligands) and (X = Cl−, NO3−). The biological activity of all the
complexes against gram-positive and gram-negative bacteria was compared with the activity of
existing standard antibacterial drugs like Linezolid and Cefaclor [Fig. 9]. Metal complexes were
found to be most potent against both gram-positive as well as gram-negative bacteria due to the
presence of thio group in the parent ligands [21].
Fig.9 [Cu(II) complex of Tetraaza macrocyclic ligand prepaired by Pallavi Goel & co
workers in 2014.
NH
HN
O
O
NH
HN
O
O
Mn
X
X
N
N
NH
HN
O
O
NH
HN
N
N
Cu
Cl
Cl
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Ajay R. Patil & co workers [22] synthesized Co(II) complexes of Schiff base 2-amino-4-
nitrophenol-N-salicylidene with some amino acids. The Schiff base and mixed ligand complexes
were preliminary scanned against various strains of microbes to study their biological effect [Fig.
10]. It has been observed that the compounds showed very good antibacterial and antifungal
activity. In comparison with the activity of ligand, activity of the metal complexes was more.
This indicated that activity increases with introduction of metal ion. The compounds showed
very good antibacterial and antifungal activity at 12.5, 25, 50, 100 and 200 ppm.
N
Co
O
NO2
HO
H
H2N
O
C
H R
O
Fig. 10 [Co(II) complexes of Schiff base 2-amino-4-nitrophenol-N-salicylidene with amino
acids was prepaired by Ajay R. Patil & co workers in 2012]
Benedict O Achugbu & co workers synthesized metal(M(II)) complexes of the Schiff base 2-(6-
methoxybenzothiazol-2-ylimino)methyl)-4-nitrophenol and characterized. The complexes
mostly exhibit good in-vitro antibacterial activities against S. aureus, E. coli and P. mirablilis
with inhibitory zones range of 16.0-27.0 mm, 13.0-15.0 mm and 17.0-20.0 mm respectively [23].
N.K. Chaudhary & co workers [24] prepared novel Schiff base ligand by condensation of 2-
aminophenol with furan-2- Carbaldehyde using distilled ethanol. The resulting solution was
allowed to evaporate by slow diffusion process in air for a week. The crystals of novel ligand
were collected, washed several times with distilled ethanol and recrystallized from hot ethanol.
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Then to make a metal complex the synthesized novel ligand in hot ethanol was added to hot
ethanolic solution of metal chlorides drop wise to make Ni(II) & Cu(II) complexes. A good
crystalline form of the complexes was obtained. Physical and analytical data suggest that the
Schiff base acts as tridentate ligand towards metal ions via azomethine-N, deprotonated-O of 2-
aminophenol and O-atom of furan moiety. The synthesized ligand, along with its metal
complexes were screened for their in-vitro antibacterial activity against four bacterial pathogens
(E. coli, Bacillus subtilis, Staphylococcus aureus and P. vulgareous ). The results of these studies
revealed that the free ligand and its metal complexes showed significant antibacterial potency
[Fig. 11].
K. S. Prasad & co workers synthesized and characterized Novel oxovanadium(IV) complexes
with 2-methyl-3-(pyridine-2-ylmethyleneamino)quinazolin-4(3H)-one or3-(2-hydroxy-3-
methoxybenzy lidene amino)-2-methylquinolin-4(3H)-one by elemental analysis [25].The
synthesized compounds were tested for antimicrobial activity by disc diffusion method. The
results indicate the enhanced activity of metal complexes over their parent ligands. The DNA
binding and nuclease activity of the synthesized compounds were also studied. The investigation
of the interaction of the complexes with calf thymus DNA has been performed with absorption
spectroscopy which showed that the complexes are avid binders of calf thymus DNA [Fig. 12].
Fig. 11[Schiff base Nickel complex prepaired using 2-aminophenol with furan-2-
Carbaldehyde by N.K.Chaudhary & co workers in 2013]
N
O
H C
O
O
C H
N
N iO
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N
N
O
N C
N
H
N
C
H
N
N
N
O
V
O
Fig.12 [oxovanadium(IV) complexes with 2-methyl-3-(pyridine-2-
ylmethyleneamino)quinazolin-4(3H)-one or3-(2-hydroxy-3-methoxybenzy lidene amino)-2-
methylquinolin-4(3H)-one, a schiff base metal complex synthesized by KS Prasad & co
workers in 2011]
K. Siddappa & co workers [26] synthesized a new compound named 3-2-(1-(1-
Hydroxynaphthalene-2-yl) Methylene amino) Phenyl) -2-Methylquinazoline-4 (3H) from hot
ethanolic solution of 3-(2-aminophenyl)-2-methylquinazolin-4(3H)-one by adding in ethanolic
solution of 2-hydroxy-1-naphtholdehyde. A general method has been used for the preparation of
complexes using the reaction of metal salts and the corresponding Schiff-base. A methanolic
solution of ligand and Cu(II), Ni(II) Co(II), Mn(II) and Zn(II) chlorides was mixed gently and
refluxed for 3 h. The complex shows good antioxidant, antitubercular and antimicrobial activities
[Fig. 13].The antibacterial and antifungal activities of the ligand and its complexes were tested
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against two gram-positive bacteria such as Staphylococcus aureus Bascillus subtilis, one gram-
negative Escherichia coli and two fungi Aspergillus niger and Aspergillus flavus & results were
found to be positive.
N
N
O
CH3
NC
H
C
HN
N
NCH3
O
O
O
M
Fig. 13 [Shiff base metal complex of 3-2-(1-(1-Hydroxynaphthalene-2-yl)
Methylene amino) Phenyl) -2-Methylquinazoline-4 synthesised by K.
Siddappa& co workers in 2013.]
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Eddie L. Chang & co workers Synthesized Schiff base of Cobalt Complexes containing a new
hybrid amine-imine-oxime ligand derived from the condensation reaction of diacetylmonoxime
with benzidine [27], & found to be effective against Bacillius subtilis [Fig. 14]. However the
same complex showed no activity towards Staphylococcus aureus or the Gram-negative bacteria
Escherichia coli and Enterobacter fecalis.
NH2 N N O-
N N NH2OH
CH3 CH3
CH3 CH3
Co LL
Fig. 14 [Cobalt Complexes of Schiff base with amine-imine-oxime ligand prepaired by
Eddie L. Chang & co workers in2010]
Mahalakshmi & co workers [28] derived the binuclear Schiff base complexes are formed newly
using different transition metals at their stable oxidation state as Cu(II), Ni(II), and VO(II).
3,3′,4,4′-tetraminobiphenyl and 2-aminobenzaldehyde were condensed to form a new Schiff base
ligand having an two N4 group responsible for better chelating to the metal centers(Fig. 15). The
free ligand and their metal complexes were screened for their antimicrobial activities against the
following species: Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus. A
comparative study of minimum inhibitory concentration (MIC) values of the Schiff base and its
complexes indicate that the metal complexes exhibit higher antibacterial activity than the free
ligand. As the test solution concentration increases, the biological activity also increases. The
minimum inhibitory concentration (MIC) values of the investigated compounds are summarized.
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The observed MIC values indicate that the complexes have higher antimicrobial activity. The
metal complexes Cu(II), Ni(II) and VO(II) have higher antimicrobial activity than the ligand.
H2N N
M
NH2N N NH2
M
N NH2
4
2 SO42-
Fig. 15 [Cu(II), Ni(II), and VO(II) schiff base complexes were prepaired by condensing
3,3′,4,4′-tetraminobiphenyl and 2-aminobenzaldehyde by Mahalakshmi & co workers in
2014]
Shakir M. Alwan & co workers made an interesting approach of synthesizing a new series of
pyridopyrimidine derivatives containing Schiff bases of certain amino acids [29]. The new
derivatives were synthesized by reacting 3-formyl-2H-pyrido pyrimidine-2, 4 (3H)-dione with
glycine, alanine, glutamic acid, histidine, tryptophan or leucine in methanol under reflux using
glacial acetic acid as catalyst. The Schiff bases showed good to moderate antibacterial activity
against the test microbes. Compounds showed also antifungal activity [Fig 16]. Compounds
showed reasonable activity against p. aurogenosa and C. albican, while it showed a good
activity against E. coli and no activity against G(-) bacteria. Compound showed a moderate
activity against E. coli and a good activity against Candida albicans. However, the Schiff bases
of the aromatic amino acids, showed better antimicrobial activities compared with those of
aliphatic amino acids.
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S.M.S.Shariar co workers [30] synthesized Schiff base Benzophenone Thiosemicarbazone
derived from thiosemicarbazide and Benzophenone & the compound was used to study their
antibacterial activities against some pathogenic bacteria by disc diffusion method. Benzophenone
thiosemicarbazone showed significant antibacterial activity as compared with that of Kanamycin.
The compounds was found to possess cytotoxic effect. Minimum inhibitory concentration of this
compound was also determined [Fig. 17]. The antibacterial activities of this compound were
measured in terms of zone of inhibition. The test compounds showed a good sensitivity against a
number of pathogenic bacteria.
D. Nasrin & co workers [31] in view of the antimicrobial activity of a series of nickel, copper
and zinc complexes of tridentate Schiff base derived from the condensation reaction of S-
benzyldithiocarbazate with 2- hydroxyacetophenone have been synthesized and found to be
potential antimicrobial agents. An attempt is also made to correlate the biological activities with
geometry of the complexes. The synthesized compounds have been evaluated for their
antibacterial and antifungal studies [Fig. 18]. The in-vitro biological screening effects of the
investigated compounds were tested against the bacterial species Shigella dysenteriae,
Salmonella typhi and Bacillus cereus and fungal species Fusarium equiseti, Macrophomina
phaseolina, Botrydiplodia theobromae and Alternaria alternate.
Karim Akbari Dilmaghania & co worker condense 5-(4-aminophenyl)-4-phenyl-1,2,4-triazole-
3-thione with 4-methoxy benzaldehyde in methanol which results in production of new Schiff
base [32].The synthesized compound were tested for their antimicrobial activity against bacterial
(Gram negative and Gram positive) strains in-vitro. The synthetic compound showed different
inhibition zones against tested bacterial strains [Fig. 19].The compound showed significant
antiproliferative activity against Acinetobacter calcoaceticus. Gajendra Kumari & co workers
[33] synthesized and characterized M(III) complexes of Cr, Mn and Fe with a Schiff base
derived from 2-amino-4-ethyl-5-hydroxybenzaldehyde and thiocarbohydrazide by several
techniques. The Schiff base ligand and the complexes were also tested for their antimicrobial
activity (against the bacteria Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa
and Bacillus megaterium, and the fungi Kluyveromyces fragilis, Rhodotorula rubra, Candida
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albicans and Trichoderma reesei) to assess their inhibiting potential[Fig 20]. An attempt was
also made to correlate the antimicrobial activity with the geometry of the complexes. All
complexes were found to be less active against the pathogens E. coli, S. aureus and
P.aeruginosa. The Cr(III) complex showed the best antimicrobial activity, but the ligand alone
was found to be active against the fungus T. reesei.
Fig. 16 [Schiff base ligand prepared by reacting 3-formyl-2H-pyrido pyrimidine-2, 4 (3H)-
dione with certain amino acids, Synthesized by Shakir M. Alwan & co workers in 2014]
C N N
H
C
S
NH2
Fig. 17 [Schiff base Benzophenone Thiosemicarbazone synthesized by S.M.S.Shariar co
workers in 2014]
N N
N
C
OHO
H R
COOH
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OH
C N
N
H
C
S
SCH2C6H5
CH3
Fig. 18 [Schiff base ligand obtained from condensation reaction of S-benzyldithiocarbazate
with 2- hydroxyacetophenone by D. Nasrin & co workers in 2013]
N
N
N S
Ph
H
N
H
R
R= 4 MeOC6H4
Fig. 19 [Schiff base ligand prepaired from 5-(4-aminophenyl)-4-phenyl-1,2,4-triazole-3-
thione with 4-methoxy benzaldehyde by Karim Akbari Dilmaghania & co worker in 2009]
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HO
C2H5
C
NH2
N
H HN
C
NH
N
S
C
H
NH2
OH
C2H5
M
H
2+
Fig. 20 [Schiff base metal M(III) complexes of Cr, Mn and Fe derived from 2-amino-4-
ethyl-5-hydroxybenzaldehyde and thiocarbohydrazide by Gajendra Kumari & co workers
in]
Azza A.A. Abou-Hussein & co worker [34] synthesized mono- and bi-nuclear acyclic and
macrocyclic complexes with hard-soft Schiff base ligand derived from the reaction of 4,6-
diacetylresorcinol and thiocabohydrazide. The Schiff base ligand and its metal complexes were
evaluated for their antimicrobial activity against one strain Gram-positive bacteria S. aureus and
P. fluorescens as Gram-negative bacteria as well as one pathogenic fungus, as F. Oxysporum.
The data were compared with standard antibiotics, chloramphencol as Gram-negative and
Cephalothin as standard reference for Gram–positive bacteria (Fig. 21). Cycloheximide was used
as antifungal standard reference. The in vitro antibacterial and antifungal activities demonstrated
that the complexes have higher antimicrobial activity in comparison with that of the ligand.
Farukh Arjmand & co -workers [35] has been synthesized the ligand by the condensation
reaction of 2-mercaptobenzimidazole and diethyloxalate. The ligand was allowed to react with
bis(ethylenediamine)CuII/ NiII complexes to yield complexes [Fig. 22].The antibacterial and
antifungal studies of the synthesized compounds were carried out against S. aureus, E. coli and
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A. niger. All the compounds tested, was found to be the most active against bacterial and three
fungal pathogens.
HO OH
N N
HN NH
S S
HN NH
N N
OHHO
Ru
Ru
Cl Cl
ClCl
Cl
Cl
Fig. 21[Schiff base metal (Ru) complex synthesized from 4,6-diacetylresorcinol and
thiocabohydrazide by Azza A.A. Abou-Hussein & co worker]
NSH
C
C
N
N
N
N
M
NH
NH
SH
Cl2
Fig.22 [Schiff base derived from condensation of 2-mercaptobenzimidazole and
diethyloxalate by Farukh Arjmand & co –workers in 2013]
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Anju Das Manikpuri & co workers Synthesis Schiff bases of Salicaldehyde and sulfonamides by
adding ethanol solution containing few drops of glacial acetic acid in to Salicaldehyde in which
sulphonamide was added slowly with constant stirring [35].The Schiff bases were screened for
the biological significance. The antimicrobial screening of duly characterized Schiff bases was
performed using paper disc method against some pathogenic strains of Salmonella entritidis and
Staphylococcus aureus (Fig. 23). Schiff bases showed significant results against S.enteritidis.
While studying the effects of concentration on zone of inhibition of each compound, the novel
Schiff bases gave excellent response against S. aureus at all chosen concentration.
N
OH
S
NH
R
O O
Fig. 23 [Schiff bases derived from Salicaldehyde and sulfonamides by Anju Das Manikpuri
& co workers in 2010]
Elsayed & co worker synthesized, characterized and evaluated biological activity of Co(II)
complexe of Schiff base Ligand Derived From Sulphadiazine and its antimicrobial activity was
found to be higher against Escherichia coli, Bacillus subtilis (G+) & Aspergillus niger and
Trechodenma viride [36]. Since, Gram-negative bacteria are considered a quantitative
microbiological method testing beneficial drugs in both experimental and clinical tumour
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
84 Scienceindoors
chemotherapy [Fig. 24]. Therefore it has been claimed that, the synthesis of these complexes
might be established a new line for search to new antitumour agents.
O
N
Co
S
NH
N N
O
O
O
O N
CH3
O
O
H2O
CH2
Fig.24 [Metal complexes Schiff bases derived from sulfagundine with Co (II) was
synthesized by Badr A. Elsayed & co worker in 2014]
Gomathi Vellaiswami & co workers [37] synthesized a novel Schiff base from 3 ethoxy salicy
aldehyde & sulpha pyridine. The orange coloured solid mass formed during refluxing was
cooled, filtered, washed and dried in a desiccator. The prepared Schiff base was characterized
and it was found that it exhibited promising antibacterial and antifungal activity against various
microorganisms [Fig. 25].
N
HN S N HC
OH
OCH2CH3
OO
Fig. 25 [Schiff base ligand , 4-(3-ethoxy-2-hydroxybenzylideneamino)-N-(pyridin-2-
yl)benzenesulfonamide prepaired from sulfapyridine and 3-ethoxysalicyl aldehyde
synthesized by Gomathi Vellaiswami & co workers in 2014]
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
85 Scienceindoors
A.V.G.S. Prasad & co-workers synthesized Schiff base from 2-thiophene- carboxy- aldehyde and
2-nitro benzoic acid. Metal complexes of the Schiff base were also prepared from salts of Mn (II)
and Co (II) in an alcoholic medium. The chemical structures of the Schiff-base ligand and its
metal complexes were confirmed by various spectroscopic studies [Fig. 26]. The free Schiff base
and its complexes have been tested for their antibacterial as well as antifungal activity by using
disc diffusion method and the results discussed. The experimental results suggested that Schiff
base derivatives are more potent in antibacterial and antifungal activities [38].
COOH
N C
SH
Fig. 26 [Schiff base derived from 2-thiophene- carboxy- aldehyde and 2-nitro benzoic acid
by A.V.G.S. Prasad & co-workers in 2014]
Conclusion
Schiff bases and their derivatives are a class of compounds with vast evidence from literature
evidence about pharmacological potential. Schiff base compounds have been shown to be
promising leads for the design of more efficient antimicrobial agents. Concisely, Schiff bases are
among the molecules which have therapeutic potential for the treatment of various human
diseases. Hence there is strong need to explore the molecular aspects of mechanism of actions of
various pharmacological mediated affected by Schiff base complexes so that we can use a huge
range of antimicrobials.
Acknowledgments
The authors would like to acknowledge M.M University, Sadopur (Ambala) for providing the
requisite facilities to perform this study.
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
86 Scienceindoors
Conflict of interest statement
There are no potential conflicts of interest among the authors regarding the publication of this
manuscript.
References
1. Katarzyna Brodowska ,Elżbieta Lodyga-Chruscinska, Schiff bases –interesting range of
applications in various fields of science, CHEMIK 2014, vol. 68,No. 2, pg. no.129–134 .
2. Anant Prakash, Devjani Adhikari, International Journal of ChemTech Research,CODEN(
USA): IJCRGG ISSN : 0974-4290, Oct-Dec2011 Vol. 3, No.4, pp 1891-1896.
3. Wenling Qin , Sha Long, Mauro Panunzio and Stefano Biondi sfff Schiff Bases: A Short
Survey on an Evergreen Chemistry Tool, Molecules 2013, 18, 12264-12289;
doi:10.3390/molecules181012264, ISSN 1420-3049.
4. Mithun Rudrapal and Biplab De,Chemistry & Biological importance of Heterocyclic Schiff
Bases, International Research Journal of Pure & Applied Chemistry, 3(3), 2013,pp 232-249.
5. S. Meenachi et al, A Review of Chemistry and Biological Importance of Schiff
Base,International Journal of Scientific Research and Reviews, IJSRR 2014 ISSN: 2279–0543,
3(1),pp 08- 18.
6. Cleiton M. da Silva, Daniel L. da Silva, Luzia V. Modolo, B. Alves Cleide V.B. Martins
Aˆ ngelo de Fa´ tima ,Schiff bases: A short review of their antimicrobial activitiesJournal of
Advanced Research, (2011) 2, 1–8.
7. A. Kaura, Lalit Sharma and V. J. Dhar , Antimicrobial Study Of Schiff Bases And Beta-
Lactam Derivatives, Int. J. Chem. Sci.: 2011, 2009-2015, 9(4), ISSN 0972-768X.
8. B.K. RAI and Rachana Kumari, Oriental Journal Of Chemistry, ISSN: 0970-020 X , CODEN:
OJCHEG, 2013, Vol. 29, No. (3),Pg.1163-1167.
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
87 Scienceindoors
9. Mustafa Yildizi, A_Kink_Raz and Ba_Aran Dulzer, Synthesis and antimicrobial activity of
new crown ethers of Schiff base type. J. Serb. Chem. Soc. 72(3) 215–224 (2007), JSCS–3551,
UDC 547.272+54–36:615.281:543.42.
10. S.Chandraleka, G.Chandramohan, D. Dhanasekaran, P. Meenakumari and A. Panneerselvam
Antifungal activity of amino acid schiff base Copper (II) complexes with phenanthroline and
bipyridyl, International Journal of Chemical and Analytical Science, ISSN: 0976-1206, 2011,
2(10), 1235-1240.
11. Gajanan M.Dongare, Synthesis, Characterisation and bacterial Screening transition metal
complexes tridentate Schiff bases of Benzene diamine, Journal of Medicinal Chemistry and Drug
Discovery,Special Issue, Analytical Chemistry Teachers And Researchers, Association, National
Convention/Seminar, , ISSN: 2347-9027,18 January 2015.
12. Muhammad Aqeel Ashraf, Karamat Mahmood, Abdul Wajid, Synthesis, Characterization
and Biological Activity of Schiff Bases,2011 International Conference on Chemistry and
Chemical Process, IPCBEE vol.10 (2011) © (2011) IACSIT Press, Singapore.
13. T. Mangamamba, M. C. Ganorkar, and G. Swarnabala, Characterization of Complexes
Synthesized Using Schiff Base Ligands and Their Screening for Toxicity Two Fungal andOne
Bacterial Species on Rice Pathogens,Hindawi Publishing Corporation International Journal of
Inorganic ChemistryVolume 2014, Article ID 736538, 22 pages.
14. Mohammed Fakruddin Al iAhmed and V.Mahammad Yunus,Microwave Synthesis &
Antimicrobial Activity of Some Cu(II),Co(II),Ni(II) & Cr(III) complexes with Schiff base 2,6-
pyridinedicarboxaldehyde Thiosemicabazone,Oriental Journal Of Chemistry(An International
Open Free Access, PeerReviewedResearchJournal) ISSN: 0970-020 X CODEN: OJCHEG,
2014, Vol. 30, No. (1): Pg. 111-117.
15. Mohammed Fakruddin Ali Ahamed, Venkatesan Jayakumar, Microwave Synthesis and
Antimicrobial Activity of Novel Metal-Complexes with Schiff Base 2, 5-Thiophene
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
88 Scienceindoors
Dicarboxaldehyde-Thiosemicarbazone , Scholars Academic Journal of Pharmacy (SAJP), Sch.
Acad. J. Pharm., 2014, ISSN 2320-4206 (Online), 3(5): 406-410.
16. R. Selwin Joseyphus and M. Sivasankaran Nair, Mycobiology, Antibacterial and Antifungal
Studies on Some Schiff Base Complexes of Zinc(II), The Korean Society of Mycology,
Mycobiology(2008),36(2), 93-98.
17. Ramasamy Jayarajan, Gnanasambandam Vasuki, and Pillutla Sambasiva Rao, Synthesis and
Antimicrobial Studies of Tridentate Schiff Base Ligands with PyrazoloneMoiety and Their Metal
Complexes Organic Chemistry, International Volume 2010, Article ID 648589, 7 pages
doi:10.1155/2010/648589.
18. M. B. Fugu, N. P. Ndahi, B. B. Paul and A. N. Mustapha,Synthesis, characterization, and
antimicrobial studies of some vanillin Schiff base metal (II) complexes Journal of Chemical and
Pharmaceutical Research, 2013, ISSN : 0975-7384, CODEN(USA) : JCPRC5, 5(4):22-28.
19. K. R. Joshi, A. J. Rojivadiya and J. H. Pandya, Synthesis and Spectroscopic and
Antimicrobial Studies of Schiff Base Metal Complexes Derived from 2-Hydroxy-3-methoxy-5-
nitrobenzaldehyde Hindawi Publishing Corporation International Journal of Inorganic
Chemistry,Volume 2014, Article ID 817412, 8 pages, http://dx.doi.org/10.1155/2014/817412.
20. E. Akila, M. Usharani, P. Maheswaran and R. Rajavel,Schiff base : A Review on their
Antimicrobial Activities, International Journal of Advanced Scientific & Technical
Research,ISSUE 3, VOL. 5,Sept-oct.2013,ISSN 2249-9954,pp: 457-469.
21. Pallavi Goel, Dinesh Kumar, Sulekh Chandra ,Schiff base ligand & their metal complexes as
anti microbial agent,Journal of chemical , biological physical science,An international peer
review E-3 journal of Science,E- ISSN:2249-1929,May 2014-july 2014,vol 4,No. 3 1946-1964,
22. Ajay R. Patil, Kamini J. Donde, Sambhaji S. Raut, Vishwanath R. Patil and Rama S.
Lokhande,Synthesis, characterization and biological activity of mixed ligand Co(II) complexes
of schiff base 2-amino-4-nitrophenol-n-salicylidene with some amino acids Journal of Chemical
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
89 Scienceindoors
and Pharmaceutical Research, ISSN : 0975-7384, CODEN(USA) : JCPRC5,2012, 4(2):1413-
1425.
23. Aderoju A Osowole, Anthony C Ekennia, and Benedict O Achugbu,
Synthesis,Characterisation &Antimicrobial Properties of some metal(II) Complexes of 2-(6-
methoxybenzothiazole-2-ylimino)methyl-4-nitrophenol,Research & Review : Journal of
Pharmaceutical Analysis, ISSN:2320-0812,April-jine 2013,vol. 2.
24. N. K. Chaudhary, In vitro antibacterial studies of some transition metal complexes of schiff
base derived from 2-aminophenol and furan-2-carbaldehyde Scholars Research Library Archives
of Applied Science Research, 2013, 5 (6):227-231.
25. KS Prasad, LS Kumar, SC Shekar, M Prasad, HD Revanasiddappa, Oxovanadium
Complexes with Bidentate N, O Ligands: Synthesis,Characterization, DNA Binding, Nuclease
Activity and Antimicrobial Studies chemical Sciences Journal, Volume 2011: CSJ-12.
26. K. Siddappa & Sunil Kumar, B Mane,Pharmacological Activity of (E) 3-2-(1-(1-
Hydroxynaphthalen-2-yl)Methyleneamino)phenyl)-2-Methylquinazoline(3H)-one Schiff base &
its transition metal complexs, Internation journal of Pharmacy & Pharmaceutical Science, ISSN
0975-1491, 2013, Vol .5 Suppl. 3,pp 725-732.
27. Eddie L. Chang , Christa Simmers and D. Andrew Knight, Cobalt Complexes as Antiviral
and Antibacterial Agents, Pharmaceuticals ISSN 1424–8247,2010, 3, 1711-1728;
doi:10.3390/ph3061711
28. N. Mahalakshmi, R. Rajavel, Synthesis, spectroscopic, DNA cleavage and antibacterial
activity of binuclear schiff base complex, Arabian journal of chemistry(2014)7, 509-517.
29. Shakir M Alwan, Jaafar Abdul-Sahib Al-Kaabi and Rafid MM Hashim, Synthesis and
Preliminary Antimicrobial Activity of New Schiff Bases of Pyrido [1,2-a] Pyrimidine
Derivatives with Certain Amino Acids, Alwan et al, ISSN: 2161-0444 Med chem 2014,
4:9,http://dx.doi.org/10.4172/2161-0444.1000206.
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
90 Scienceindoors
30. S. M. S. Shariar, M. Jesmin, M. M. Ali, Antibacterial Activities of Some Schiff Bases
Involving Thiosemicarbazide and Ketones, International Letters of Chemistry, Physics and
Astronomy, ISSN 2299-3843, 7 (2014) 53-61.
31. D. Nasrin,M. Ashraful Alam, M. Nazmul Hossain and M. Nazimuddin,
Synthesis,Characterisation & antimicrobial activity of Schiff Base metal complexes derived from
S-benzyldithiocarbazate with 2-hydroxyacetophenone. D. Nasrin el al / Chemistry Journal ISSN
2049-954X (2013), Vol. 03, Issue 01, pp. 13-19.
32. Karim Akbari Dilmaghania, Fazel Nasuhi Purb and Mahnaz Hatami Nezhada, Synthesis and
Antibacterial Evaluation of New Thione Substituted 1,2,4-Triazole Schiff Bases as Novel
Antimicrobial Agents.
33. Gajendra Kumari, Dharmendra Kumar, C. P. Singh, Amit Kumar and V. B. Rana
,Synthesis,characterization & antimicrobial activity of Trivalent metal Schiff base complexes.
Journal of Serbian Chemical Society, J. Serb. Chem. Soc. 75 (5) 629–637 (2010) , JSCS–3993,
UDC 546.733’763’723’+542.9+ 547.571+547.511:615.28–188.
34. E. Akila, M. Usharani, P. Maheswaran and R. Rajavel,Schiff base : A Review on their
Antimicrobial Activities, International Journal of Advanced Scientific & Technical Research,
ISSN 2249-9954, ISSUE 3, VOL. 5 ,Sept-oct.2013.
35.Anju Das Manikpuri,Synthesis and antimicrobial studies on therapeutically significant Schiff
bases of Salicaldehyde and sulfonamides,Research Journal of Pharmaceutical, Biological and
Chemical Sciences, ISSN: 0975-8585, Volume 1 Issue 2 Page No. 21.
36. Badr A. Elsayed,Synthesis,characterization,Antimicrobial & cytotoxic studies on some novel
transition metal complexes of Schiff base ligand derived fromSulfadiazine with molecular orbital
calculations, International Journal of Chemistry and Materials Research, 2014, 2(1): 1-16.
Journal of Biological and Chemical Sciences (JBCS) Rani et al, (2015) vol.2, no. 1, 62-91
91 Scienceindoors
37. Gomathi VellaIswami & Selvameena Ramaswamy,Synthesis,Spectral characterization &
antimicrobial Screening of novel Schiff base from Sulfa Drugs, International Journal of
Pharmacy and Pharmaceutical Sciences, ISSN- 0975-1491, 2014, Vol 6, Issue 1.
38. A.V.G.S. Prasad, P. Venkateswara Rao, P.S.S. Prasad, Spectral and Biological studies of
Manganese (II) and Cobalt (II) Complexes with Schiff Base Derived from 2-
Thiophenecarboxylaldehyde and 2-nitrobenzoic Acid,International Journal for Pharmaceutical
Research Scholars (IJPRS), ISSN No: 2277 – 7873, 2014, V-3, I-1,pp 91-94.