Cancer is one of the most serious medical problem and second leading cause of death in the world, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of ...cellular differentiation and uncontrolled cellular growth. The benzimidazole is a heterocyclic moiety found in extensive number of natural and biological active molecules. Benzimidazole derivatives might be considered as auxiliary isosters of nucleotides having attached heterocyclic cores in their structures, cooperate effortlessly with biopolymers and have potential action for chemotherapeutic applications. Benzimidazole and its derivatives displayed a wide range of biological activity because of its structural similarity with the naturally occurring nucleotides. Benzimidazole has established huge alertness in current time and is extremely significant heterocyclic pharmacophore in recent drug innovation and medicinal chemistry. The present review summarizes the chemistry of various substituted benzimidazole derivatives with their antiproliferative significance towards the various cancer cell lines such as HCT116, MCF7, HeLa, HepG2, A549 and A431.
Heterocyclic compounds are inevitable in a numerous part of life sciences. These molecules perform various noteworthy functions in nature, medication and innovation. Nitrogen-containing heterocycles ...exceptionally azoles family are the matter of interest in synthesis attributable to the way that they happen pervasively in pharmacologically dynamic natural products, multipurpose arranged useful materials also profoundly powerful pharmaceuticals and agrochemicals. Benzimidazole moiety is the key building block for several heterocyclic scaffolds that play central role in the biologically functioning of essential molecules. They are considered as promising class of bioactive scaffolds encompassing diverse varieties of activities like antiprotozoal, antihelminthic, antimalarial, antiviral, anti-inflammatory, antimicrobial, anti-mycobacterial and antiparasitic. Therefore in the present review we tried to compile the various pharmacological activities of different derivatives of heterocyclic benzimidazole moiety.
Thiazolidinediones are sulfur containing pentacyclic compounds that are widely found throughout nature in various forms. Thiazolidinedione nucleus is present in numerous biological compounds, e.g., ...anti-malarial, antimicrobial, anti-mycobacterium, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antitubercular agent. However, owing to the swift development of new molecules containing this nucleus, many research reports have been generated in a brief span of time. Therefore seems to be a requirement to collect recent information in order to understand the current status of the thiazolidinedione nucleus in medicinal chemistry research, focusing in particular on the numerous attempts to synthesize and investigate new structural prototypes with more effective antidiabetic, antimicrobial, antioxidant, anti-inflammatory, anticancer and antitubercular activity.
Background
Benzimidazole is a heterocyclic moiety whose derivatives are present in many of the bioactive compounds and posses diverse biological and clinical applications. Benzimidazole agents are ...the vital pharmacophore and privileged sub-structures in chemistry of medicine. They have received much interest in drug discovery because benzimidazoles exhibited enormous significance. So attempts have been made to create repository of molecules and evaluate them for prospective inherent activity. They are extremely effective both with respect to their inhibitory activity and favorable selectivity ratio.
Conclusion
Benzimidazole is most promising category of bioactive heterocyclic compound that exhibit a wide variety of biological activities in medicinal field. The present review only focus on antimicrobial activity of reported benzimidazole derivatives may serve as valuable source of information for researchers who wish to synthesize new molecules of benzimidazole nucleus which have immense potential to be investigated for newer therapeutic possibilities.
Background
A new series of benzoxazole analogues was synthesized and checked for their in vitro antibacterial, antifungal and anticancer activities.
Results and discussion
The synthesized benzoxazole ...compounds were confirmed by IR,
1
H/
13
C-NMR, mass and screened for their in vitro antimicrobial activity against Gram-positive bacterium:
Bacillus subtilis
, four Gram-negative bacteria:
Escherichia coli
,
Pseudomonas aeruginosa
,
Klebsiella pneumoniae
,
Salmonella typhi
and two fungal strains:
Candida albicans
and
Aspergillus niger
using tube dilution technique and minimum inhibitory concentration (MIC) was noted in µM and compared to ofloxacin and fluconazole. Human colorectal carcinoma (HCT116) cancer cell line was used for the determination of in vitro anticancer activity (IC
50
value) by Sulforhodamine B assay using 5-fluorouracil as standard drug.
Conclusion
The performed study indicated that the compounds
1
,
10
,
13
,
16
,
19
,
20
and
24
had highest antimicrobial activity with MIC values comparable to ofloxacin and fluconazole and compounds
4
,
6
,
25
and
26
had best anticancer activity in comparison to 5-fluorouracil.
Background
Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms ...i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-
urease
, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.
Methods
The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (
B. subtilis
), Gram-negative (
P. aeruginosa
and
E. coli
) bacterial and fungal (
C. albicans
and
A. niger
) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-
urease
screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.
Results, discussion and conclusion
The biological screening results reveal that the compounds
T
5
(MIC
BS
,
EC
= 24.7 µM, MIC
PA
,
CA
= 12.3 µM) and
T
17
(MIC
AN
= 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MIC
Cipro
= 18.1 µM, MIC
Amo
= 17.1 µM) and fluconazole (MIC
Flu
= 20.4 µM), respectively. The antioxidant evaluation showed that compounds
T
2
(IC
50
= 34.83 µg/ml) and
T
3
(IC
50
= 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC
50
= 35.44 µg/ml). Compounds
T
3
(IC
50
= 54.01 µg/ml) was the most potent
urease
inhibitor amongst the synthesized compounds and compared to standard thiourea (IC
50
= 54.25 µg/ml). The most potent anticancer activity was shown by compounds
T
2
(IC
50
= 3.84 μM) and
T
7
(IC
50
= 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC
50
= 25.36 μM).
Background
Thiazolidinedione is a pentacyclic moiety having five membered unsaturated ring system composed with carbon, oxygen, nitrogen and sulfur molecules at 1 and 3 position of the thiazole ring ...and widely found throughout nature in various form. They favourably alter concentration of the hormones secreted by adipocytes, particularly adiponectin. They also increase total body fat and have mixed effects on circulating lipids. Thiazolidinedione nucleus is present in numerous biological moieties and has different pharmacological activities likes, e.g. antimalarial, antimicrobial, antimycobacterial, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antituberculosis.
Results and discussion
The synthesized compounds were screened for their in vitro antimicrobial potential against Gram (positive and negative) bacterial and fungal strains by tube dilution technique. In this series, compound
10
exhibited significant antimicrobial activity against
B
.
subtilis
and
S
.
aureus
with MIC = 4.2 × 10
−2
µM/ml, compound
15
showed significant activity against
K
.
pneumonia
with MIC = 2.60 × 10
−2
µM/ml and compound
4
displayed potent antibacterial activity against
E
.
coli
with MIC = 4.5 × 10
−2
µM/ml. Compound
10
had most potent antifungal activity against
C
.
albicans
and
A
.
niger
with MIC = 4.2 × 10
−2
µM/ml. Compounds
12
and
15
were found as most active antidiabetic agents having IC
50
= 27.63 μg/ml and 22.35 μg/ml, respectively, using DPPH assay. Antioxidant activity results indicated that compounds
3
and
9
displayed good antioxidant agent with IC
50
= 29.04 μg/ml and 27.66 μg/ml respectively, using
α amylase
assay.
Conclusion
All the synthesized derivatives exhibited good antimicrobial, antidiabetic and antioxidant activities using specific methods then compared with mentioned standard drugs. Especially, compounds
3
,
4
,
9
,
10
,
12
and
15
displayed highest activity. Structure activity relationship demonstrated that presence of electron withdrawing group (
o
-NO
2
,
p
-Cl,
p
-Br) enhanced the antibacterial activity against
E. coli
as well as increased the antioxidant activity while the presence of electron releasing group (
o/p
-OCH
3
, 3,4,5-trimethoxy) enhanced the antibacterial activity against
S. aureus
,
B. subtilis
,
S
.
typhi
,
K
.
pneumonia
,
C
.
albicans
and
A
.
niger
as well as the antidiabetic activity.
Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity. Molecular docking technique is routinely used in modern drug discovery ...for understanding the drug-receptor interaction. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against cancer cell lines (HCT116 and MCF7) by sulforhodamine B (SRB) assay. Further, molecular docking study of data set was carried out by Schrodinger-Maestro
v11.
5 using CDK-8 (PDB code: 5FGK) and ER-alpha (PDB code: 3ERT) as possible target for anticancer activity. Molecular docking results demonstrated that compounds
12
,
16
,
N9
,
W20
and
Z24
displayed good docking score with better interaction within crucial amino acids and corelate to their anticancer results. ADME results indicated that compounds
16
,
N9
and
W20
have significant results within the close agreement of the Lipinski’s rule of five and Qikprop rule within the range and these compounds may be taken as lead molecules for the discovery of new anticancer agents.
Various analogues of benzimidazole are found to be biologically and therapeutically potent against several ailments. Benzimidazole when attached with heterocyclic rings has shown wide range of ...potential activities. So, from the above provided facts, we altered benzimidazole derivatives so that more potent antagonists could be developed. In the search for a new category of antimicrobial and anticancer agents, novel azomethine of 2-mercaptobenzimidazole derived from 3-(2- (1H-benzodimidazol-2-ylthio)acetamido)benzohydrazide were synthesized.
The synthesized analogues were characterized by FT-IR,
H/
C-NMR and MS studies as well C, H, N analysis. All synthesized compounds were evaluated for in vitro antibacterial activity against Gram-positive (B. subtilis), Gram-negative (E. coli, P. aeruginosa, K. pneumoniae and S. typhi) strains and in vitro antifungal activity against C. albicans and A. niger strains by serial dilution method, the minimum inhibitory concentration (MIC) described in μM/ml. The in vitro anticancer activity of synthesized compounds was determined against human colorectal carcinoma cell line (HCT- 116) using 5-fluorouracil as standard drug.
In general, most of the synthesized derivatives exhibited significant antimicrobial and anticancer activities. Compounds 8, 10, 15, 16, 17, 20 and 22 showed significant antimicrobial activity towards tested bacterial and fungal strains and compound 26 exhibited significant anticancer activity.
Being derived from primary amine and aromatic aldehyde, Schiff base and their complexes have an imperative role in the improvement of inorganic chemistry, which are broadly studied as coordination ...compounds and are gradually becoming more important in biochemical and analytical applications.
They have also been used for antibacterial, antifungal, anticancer, antitubercular activities. Novel synthesised Schiff's base 2-methoxy-4-((3-methylpyridin-2-ylimino)methyl)phenol (SB) and its metal complexes (ZnII, CuII, CoII and NiII) were characterised by UV, IR and NMR spectroscopy. Formation of the Schiff base and the metal (ZnII, CuII, CoII and NiII) chelates was supported by spectral and analytical data. The ligand and metal complexes have been screened for their antibacterial activity against Staphylococcus aureus, Salmonella typhi, Escherichia coli, Klebsiella pneumoniae and antifungal activity against the fungi Candida albicans and Aspergillus niger. Further, the synthesised compounds were also screened for antiproliferative activity against the human colorectal carcinoma (HCT116) cell line using the Sulforhodamine B assay.
Metal complexes formed were found to enhance the potency of the Schiff base due to coordination with a copper complex, showing better activity than others.
Copper complex was observed to be more potent than other complexes against all the pathogenic microbes and cancer cell line (HCT116).
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