Abstract:Chemistry of 2-aminothiophenes is arguably one of the most extensive and dynamic field of present-day thiophene research. Since 1961 when first report on the Gewald reaction was reported it became a universal method for synthesis of substituted 2-aminothiophenes and has gained prominence in recent times. The availability of reagents and the mild reaction conditions all contribute to the versatility of this reaction. This review summarizes the synthetic strategies for substituted 2-aminothiophenes. Consequently… Show more
“…Although molecular modification is currently the most commonly used strategy to improve the physicochemical and pharmacological properties of drugs [36], this study showed that the association of a novel 2-aminothiophene derivative with cyclodextrin seems to be an efficient alternative to improve their anti-proliferative activity against tumor cells.…”
The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.
“…Although molecular modification is currently the most commonly used strategy to improve the physicochemical and pharmacological properties of drugs [36], this study showed that the association of a novel 2-aminothiophene derivative with cyclodextrin seems to be an efficient alternative to improve their anti-proliferative activity against tumor cells.…”
The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.
“…2). The amine, tetrahydrobenzothiophene used for synthesis of derivative DS-2 was prepared by the Gewald reaction [29]. The amines used for the synthesis of DS-3 , DS-5 and DS-7 were prepared by the reaction of aliphatic/aromatic carboxylic acids with the POCl 3 and thiosemicarbazide as per the reported methods [30, 31].…”
Background
In search of effective antimicrobial and cytotoxic agents, a series of indole hybridized diazenyl derivatives (
DS-1
to
DS-21
) was efficiently prepared by condensation of diazotized
p
-aminoacetophenone with indole or nitroindole followed by reaction with different aromatic/heteroaromatic amines of biological significance. The synthesized derivatives were characterized by various spectroscopic techniques.
Methodology
The antimicrobial evaluation of
DS-1
to
DS-23
was done by tube dilution method against various pathogenic bacterial and fungal strains. The active antimicrobial derivatives were further evaluated for cytotoxicity against human lung carcinoma cell line (HCT-116), breast cancer cell line (MDAMB231), leukemic cancer cell line (K562), and normal cell line (HEK293) by MTT assay using doxorubicin as the standard drug. The test derivatives were additionally docked for the B-subunit of enzyme DNA gyrase from
E. coli
at the ATPase binding site to study the molecular interactions using Schrodinger maestro
v11.5
software.
Results and discussion
Most of the synthesized derivatives have shown high activity against Gram-negative bacteria particularly
E. coli
and
K. pneumonia
with MIC ranging from 1.95 to 7.81 μg/ml. The derivatives have demonstrated very less activity against tested Gram positive bacterial and fungal strains. The derivatives
DS-14
and
DS-20
have been found to active against breast cancer cell line and human colon carcinoma cell line having IC
50
in the range of 19–65 µg/ml. All the derivatives were found to less potent against leukemic cancer cell line. The synthesized derivatives have revealed their safety by exhibiting very less cytotoxicity against the normal cell line (HEK-293) with IC
50
> 100 µg/ml. Most of the active derivatives have shown good docking scores in comparison to the standard drugs against DNA gyrase from
E. coli
. Further ADME predictions by Qikprop module of the Schrodinger confirmed these molecules have drug like properties.
Conclusion
The derivatives
DS-14
and
DS-20
have shown potential against Gram-negative bacteria and breast cancer cell line and can be used as a lead for rational drug designing of the antimicrobial and cytotoxic agents.
.
“…The structural confirmation of the target compounds was carried out by FTIR, UV–vis, NMR, mass spectroscopy, and elemental analysis. The thiophene substituted amines used in the reaction were prepared by the reported Gewald procedure [35]. The derivatives NS-3 , NS-17 , NS-18 , NS-19 , and NS-20 have not been mentioned in the scheme as these derivatives did not meet the purity requirements for structural agreement by spectral techniques.Fig.…”
Background
In search of new antimicrobial and cytotoxic agents, a series of new naphthol diazenyl scaffold based Schiff bases (
NS1
–
NS23
) was efficiently synthesized by condensation of 2-hydroxy naphthaldehyde azo dyes with various substituted aromatic/heteroaromatic/aliphatic amines.
Methodology
The synthesized derivatives were characterized by various physicochemical and spectral techniques and assessed for in vitro antimicrobial and cytotoxic potential against human colorectal carcinoma cell line (HT-29). The active derivatives were further evaluated for their apoptotic potential by Annexin-V/propidium iodide double staining assay using flow cytometer and analyzed for cell-cycle arrest studies.
Results and conclusion
The derivative
NS-2
was found maximum active against
E
.
coli
,
S. enterica
and
B. subtilis
. The derivatives
NS-12
,
NS-15
,
NS-21
, and
NS-23
showed maximum antifungal activity against
A. fumigatus
. The maximum cytotoxicity was observed from the derivatives
NS-2
,
NS-8
,
NS-21
, and
NS-23
towards HT-29 cell line with IC
50
between 4 and 19 μg/ml. More than 90% and 62% of the cells were found in the apoptotic phase on treatment with
NS-2
and
NS-21
respectively in comparison to the 68% for doxorubicin. Further, these derivatives arrested the cell growth in S and G2/M phase of the cell cycle.
Electronic supplementary material
The online version of this article (10.1186/s13065-019-0558-y) contains supplementary material, which is available to authorized users.
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