Synthesis, characterization and biological studies of Schiff bases derived

from heterocyclic moiety

Some new Schiff bases (H1-H7) have been synthesized by the condensation of 2-
aminophenol, 2-amino-4-nitrophenol, 2-amino-4-methylphenol, 2-amino benzimidazole
with thiophene-2-carboxaldehyde and pyrrole-2-carboxaldehyde. The structures of newly
synthesized compounds were characterized by elemental analysis, FT-IR, 1 H NMR, UV–
VIS, and single crystal X-ray crystallography. The in vitro antibacterial activity of the
synthesized compounds has been tested against Salmonella typhi, Bacillus
coagulans, Bacillus pumills, Escherichia coli, Bacillus circulans, Pseudomonas,
Clostridium and Klebsilla pneumonia by disk diffusion method. The quantitative
antimicrobial activity of the test compounds was evaluated using Resazurin based Microtiter
Dilution Assay. Ampicillin was used as standard antibiotics. Schiff bases individually
exhibited varying degrees of inhibitory effects on the growth of the tested bacterial species.
The antioxidant activity of the synthesized compounds was determined by the 1,1-diphenyl-
2-picrylhydrazyl(DPPH) method. IC50 value of synthesized Schiff bases were calculated and
compared with standard BHA.

In recent years, the number of people suffering from

cancer and multidrug-resistant infections has sharply
increased, leaving humanity without any choice but to
search for new treatment options and strategies. Al-
though cancer is considered the leading cause of death
worldwide, it also paves the way many microbial
infections and thus increases this burden manifold.
Development of small molecules as anticancer and
anti-microbial agents has great potential and a plethora of
drugs are already available to combat these dis-
eases. However, the wide occurrence of multidrug
resistance in both cancer and microbial infections ne-
cessitates the development of new and potential
molecules with desired properties that could circumvent
the multidrug resistance problem. A successful strategy in
anticancer chemotherapy has been the use of
metallo-drugs and this strategy has the potential to be
used for treating multidrug-resistant infections more
efficiently. As a class of molecules, Schiff bases have
been the topic of considerable interest, owing to their
versatile metal chelating properties, inherent biological
activities and flexibility to modify the structure to
fine-tune it for a particular biological application. Schiff
base-based metallo-drugs are being researched to
develop new anticancer and anti-microbial
chemotherapies and because both anticancer and anti-
microbial targets are different, heterocyclic Schiff bases
can be structurally modified to achieve the desired
molecule, targeting a particular disease. In this review, we
collect the most recent and relevant literature
concerning the synthesis of heterocyclic Schiff base metal
complexes as anticancer and anti-microbial
agents and discuss the potential and future of this class of
metallo-drugs as either anticancer or anti-
n recent years, the number of people suffering from
cancer and multidrug-resistant infections has sharply
increased, leaving humanity without any choice but to
search for new treatment options and strategies. Al-
though cancer is considered the leading cause of death
worldwide, it also paves the way many microbial
infections and thus increases this burden manifold.
Development of small molecules as anticancer and
anti-microbial agents has great potential and a plethora of
drugs are already available to combat these dis-
eases. However, the wide occurrence of multidrug
resistance in both cancer and microbial infections ne-
cessitates the development of new and potential
molecules with desired properties that could circumvent
the multidrug resistance problem. A successful strategy in
anticancer chemotherapy has been the use of
metallo-drugs and this strategy has the potential to be
used for treating multidrug-resistant infections more
efficiently. As a class of molecules, Schiff bases have
been the topic of considerable interest, owing to their
versatile metal chelating properties, inherent biological
activities and flexibility to modify the structure to
fine-tune it for a particular biological application. Schiff
base-based metallo-drugs are being researched to
develop new anticancer and anti-microbial
chemotherapies and because both anticancer and anti-
microbial targets are different, heterocyclic Schiff bases
can be structurally modified to achieve the desired
molecule, targeting a particular disease. In this review, we
collect the most recent and relevant literature
concerning the synthesis of heterocyclic Schiff base metal
complexes as anticancer and anti-microbial
agents and discuss the potential and future of this class of
metallo-drugs as either anticancer or anti
Heterocyclic Schiff base transition metal complexes in antimicrobial and
anticancer chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
Heterocyclic Schiff
base transition metal
complexes in
antimicrobial and
anticancer
chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
Heterocyclic Schiff
base transition metal
complexes in
antimicrobial and
anticancer
chemotherapy
Heterocyclic Schiff
base transition metal
complexes in
antimicrobial and
anticancer
chemotherapy
Heterocyclic Schiff base
transition metal
complexes in antimicrobial
and anticancer
chemotherapy
In recent years, the number of people suffering from
cancer and multidrug-resistant infections has sharply
increased, leaving humanity without any choice but to
search for new treatment options and strategies. Al-
though cancer is considered the leading cause of death
worldwide, it also paves the way many microbial
infections and thus increases this burden manifold.
Development of small molecules as anticancer and
anti-microbial agents has great potential and a plethora of
drugs are already available to combat these dis-
eases. However, the wide occurrence of multidrug
resistance in both cancer and microbial infections ne-
cessitates the development of new and potential
molecules with desired properties that could circumvent
the multidrug resistance problem. A successful strategy in
anticancer chemotherapy has been the use of
metallo-drugs and this strategy has the potential to be
used for treating multidrug-resistant infections more
efficiently. As a class of molecules, Schiff bases have
been the topic of considerable interest, owing to their
versatile metal chelating properties, inherent biological
activities and flexibility to modify the structure to
fine-tune it for a particular biological application. Schiff
base-based metallo-drugs are being researched to
develop new anticancer and anti-microbial
chemotherapies and because both anticancer and anti-
microbial targets are different, heterocyclic Schiff bases
can be structurally modified to achieve the desired
molecule, targeting a particular disease. In this review, we
collect the most recent and relevant literature
concerning the synthesis of heterocyclic Schiff base metal
complexes as anticancer and anti-microbial
agents and discuss the potential and future of this class of
metallo-drugs as either anticancer or anti-
In recent years, the number of people suffering from cancer and multidrug-resistant infections has
sharply increased, leaving humanity without any choice but to search for new treatment options and
strategies. Although cancer is considered the leading cause of death worldwide, it also paves the way
many microbial infections and thus increases this burden manifold. Development of small molecules as
anticancer and anti-microbial agents has great potential and a plethora of drugs are already available to
combat these diseases. However, the wide occurrence of multidrug resistance in both cancer and
microbial infections necessitates the development of new and potential molecules with desired
properties that could circumvent the multidrug resistance problem. A successful strategy in anticancer
chemotherapy has been the use of metallo-drugs and this strategy has the potential to be used for
treating multidrug-resistant infections more efficiently. As a class of molecules, Schiff bases have been
the topic of considerable interest, owing to their versatile metal chelating properties, inherent biological
activities and flexibility to modify the structure to fine-tune it for a particular biological application.
Schiff base-based metallo-drugs are being researched to develop new anticancer and anti-microbial
chemotherapies and because both anticancer and antimicrobial targets are different, heterocyclic Schiff
bases can be structurally modified to achieve the desired molecule, targeting a particular disease. In this
review, we collect the most recent and relevant literature concerning the synthesis of heterocyclic Schiff
base metal complexes as anticancer and anti-microbial agents and discuss the potential and future of
this class of metallo-drugs as either anticancer or antimicrobial agents.

n recent years, the number of people suffering from

cancer and multidrug-resistant infections has sharply
increased, leaving humanity without any choice but to
search for new treatment options and strategies. Al-
though cancer is considered the leading cause of death
worldwide, it also paves the way many microbial
infections and thus increases this burden manifold.
Development of small molecules as anticancer and
anti-microbial agents has great potential and a plethora of
drugs are already available to combat these dis-
eases. However, the wide occurrence of multidrug
resistance in both cancer and microbial infections ne-
cessitates the development of new and potential
molecules with desired properties that could circumvent
the multidrug resistance problem. A successful strategy in
anticancer chemotherapy has been the use of
metallo-drugs and this strategy has the potential to be
used for treating multidrug-resistant infections more
efficiently. As a class of molecules, Schiff bases have
been the topic of considerable interest, owing to their
versatile metal chelating properties, inherent biological
activities and flexibility to modify the structure to
fine-tune it for a particular biological application. Schiff
base-based metallo-drugs are being researched to
develop new anticancer and anti-microbial
chemotherapies and because both anticancer and anti-
microbial targets are different, heterocyclic Schiff bases
can be structurally modified to achieve the desired
molecule, targeting a particular disease. In this review, we
collect the most recent and relevant literature
concerning the synthesis of heterocyclic Schiff base metal
complexes as anticancer and anti-microbial
agents and discuss the potential and future of this class of
metallo-drugs as either anticancer or anti
Intensive research efforts all over the world are ongoing, in order to explore benign and effective
metal-based biologically active compounds as potential antimicrobial drugs. Among the different
therapeutic approaches to wipe out these microbial menaces, the assessment of using transition
metal complexes as metallo-drugs has shown them to have great potential. Metal complexes are
supposed to exert their effect by inhibition of enzymes, interaction with intracellular
biomolecules, enhanced lipophilicity, alteration of cell membrane functions, arrest of the cell
cycle, etc.8 Due to a wide variety of coordination spheres, ligand designs, oxidation states and
redox potentials, metal complexes are supposed to alter the kinetic and thermodynamic
properties of the complexes towards biological receptors. Thus, chelation causes drastic changes
in the biological properties of ligands as well as the metal moiety. Many metal complexes of the
quinoline group of antibiotics, viz. ciprofloxacin, norfloxacin and tetracycline, were evaluated
and reported to possess enhanced activity compared to antibiotics alone.9–11 Recently, a
bismuth–norfloxacin complex was reported to possess enhanced antimicrobial activity compared
to norfloxacin alone.12 It is believed that the enhanced activity is due to increased bioavailability
of the complex. Hence, transportation of organic ligands into bacterial cells can be facilitated by
the formation of metal complexes. The PdIJII) complex of doxycycline is two times more potent
than doxycycline alone against the resistant strain E. coli HB101/pBR322.13 Many reports on
Schiff base (SB) transition metal complexes explicate their efficient bioactivity against a range
of bacterial and fungal species. In particular, heterocyclic Schiff base (HSB) metal complexes
have dominated medicinal chemistry due to their wide range of properties.14,15 SB complexes
tethered with heterocyclic moieties like 4-aminoantipyrine, pyrazole, 1,2,4-triazoles,
benzoxazole, triazines, and coumarins have received remarkable interest as broad-spectrum
antibacterial, antifungal and antiviral agents. The huge enthusiasm for the preparation of HSB
compounds is associated with the extraordinary properties that the heterocyclic system imparts to
such ligands and to their metal complexes. Besides antimicrobial infections, medicinal chemists
are also facing great challenges in pacifying the inconvenience caused by cancer. The
widespread success of cisplatin against several types of cancers has placed metal-based drugs in
the frontline in the fight against cancer.28,29 Although highly effective in treating a variety of
cancers, cisplatin shows doselimiting side effects30 and drug resistance, which is only partially
amended by employment of new platinum drugs.31–34 These problems have stimulated an
extensive search and prompted chemists to develop alternative strategies, based on different
ligands and metals, with improved pharmacological properties and aimed at different targets.35
This review dHeterocyclic Schiff base chemistry is one of the attractive and challenging fields in current
medical science. Due to expanded range of applications, medicinal chemistry has grown actively into the most
active research area. Heterocyclic Schiff base derivatives are the most extensively used organic compounds
with broad range of applications used as pigments, dyes, catalysts, and intermediates in many organic reactions
[1, 2]. They showed phototropism and thermochromism in the solid state used in optical and electrochemical
sensors for the detection and enhancement of selectivity and sensitivity [3, 4]. Due to their applications in
biological, analytical, and medicinal field, and their role as catalysts in organic synthesis, heterocyclic Schiff
bases are considered as one of the most potential groups of heterocyclic compounds [ 5]. The presence of
azomethine group in heterocyclic Schiff base derivatives makes it very critical for various biological
applications such as antifungal [6, 7], antibacterial [8, 9], antiproliferative [10], anticoagulant [11], anti-
inflammatory [12], and antiviral [13] agents. They have been widely used in coordination chemistry mainly
due to their facile synthesis, electronic properties, and good solubility in common solvents [14].
Heterocyclic tridentate Schiff base ligands, with a flexible atom, are better in comparison with bidentate
ligand, and their chelating power makes them suitable ligands for stabilizing transition metals in various
oxidation states and in wide range of catalytic transformations. They have been used extensively in
biochemistry, material science, hydrometallurgy, catalysis and separation phenomena, and many of the
biological processes [15, 16]. Due to their thermal stability, biological applications, and presence of nitrogen
atom in aromatic ring, pyridine and pyrimidine-based heterocyclic compounds are considered to be better
ligands [17].
Since DNA and genetic material contain all cellular information, the study of DNA interaction is a very
important aspect at present. Interaction of small molecules with DNA has been investigated and it attracted
more attention for the designing of more effective drugs which target to DNA. Classical and nonclassical
intercalation and groove or electrostatic modes of binding have been studied by various interaction modes of
drug-DNA [18–22]. Free radicals were mostly generated in various bio-oxidative processes that damage
various body components such as fat and proteins and cause various harmful diseases such as cancer,
hypertension, Parkinson’s disease, and Alzheimer’s disease. Therefore, to develop new therapeutic drugs to
neutralize the effect or damage caused by free radicals is to achieve more attention [23–26].
In literature, an antioxidant activity evaluation of heterogeneous ring derivatives using hydrogen peroxide and
DPPH radicals was reported free in various ways and many of these compounds act as good antioxidants.
Thus, to know how these antioxidant compounds work is very essential [27]. Diseases spread by bacteria are
most common, and the mortality rate associated with bacterial infections increases day by day. Lack of
medicinal treatment is the prime cause related to bacterial infections due to the resistance of bacteria to
antibiotics. Therefore, it is a special need to develop new antimicrobial agents. Hence, researchers have been
working for last many years to find new antibacterial agents due to the development of bacterial resistance
[28].
So in this regard, we have tried to develop such types of heterocyclic derivatives which can bind easily with
DNA and significant antioxidant to prevent damage caused by free radicals [29]; herein, we reported synthesis
of unknown p-dimethylaminobenzaldehyde derivatives 1–8 and screened their DNA binding, fluorescence
quenching, and antioxidant and antimicrobial assays. In addition, in this work, we calculated some molecular
docking parameters of compounds in order to correlate them with their antimicrobial activity.
escribes advances in the synthesis, design, and