A library of 3-(5-(substituted benzyl)sulfanyl-1,3,4-oxadiazol-2-yl)-
N
-substituted pyridine-2-amines and 2-(5-{2-(substituted phenyl)aminopyridin-3-yl}-2,3-dihydro-1,3,4-oxadiazol-2-yl)sulfanyl-
N
...-substituted phenylacetamides were synthesized by the multistage procedure, starting from 2-chloronicotinic acid. The newly synthesized compounds were tested for
in vitro
cytotoxicity against the MCF-7 breast cancer cell line. Significant cell death rates were demonstrated by all the test compounds in a concentration-dependent manner. The active compounds
N
-(4-fluorophenyl)-3-{5-(4-nitrobenzyl)sulfanyl-1,3,4-oxadiazol-2-yl}pyridin-2-amine and 2-(5-{2-(3-chloro-4-fluorophenyl)aminopyridin-3-yl}-1,3,4-oxadiazol-2-yl)sulfanyl-
N
-(2,4-dichlorophenyl)-acetamide were further subjected to DAPI staining to assess their effect on nuclear fragmentation. Additionally, the synthesized compounds were screened for anti-inflammatory and antioxidant activities, yielding promising results. A molecular docking study was conducted to assess the binding affinities of the synthesized compounds to PDB 3ERT (human estrogen receptor-α in complex with 4-hydroxytamoxifen). For all the compounds, good binding energies with the target protein were predicted. An ADME screening showed that the majority of the synthesized compounds have good pharmacokinetic profiles.
This study describes the synthesis and characterization of some 1-(2,7-dichloro-9-(1,3-diphenyl-1
H
-pyrazol-4-yl)methylene-9
H
-fluoren-4-yl)-2-(methylselenyl)-ethanols and their biological ...evaluation as antimicrobial agents. The synthesis of the target compounds requires two key starting materials, 1-2,7-dichloro-9
H
-fluoren-4-yl-2-(methylselanyl)ethan-1-ol and various 1,3-diarylpyrazole-4-carboxaldehydes. The key intermediates, 1,3-diarylpyrazole-4-carboxaldehydes were prepared by the Vilsmeier-Haack reaction. Finally, the target compounds were obtained by a simple Knoevenagel condensation. The structures of the newly synthesized compounds were established based on spectral techniques. The synthesized compounds were screened for their in vitro antibacterial, antifungal, and anti-inflammatory activities. All the compounds were tested for their preliminary cytotoxicity by hemolysis assay. The microbial growth inhibition was also investigated via in silico molecular docking studies.
Graphical abstract
2-Amino-5-(3-fluoro-4-methoxyphenyl)thiophene-3-carbonitrile have been synthesized from 1-(3-fluoro-4-methoxyphenyl)ethanone, malononitrile, a mild base and sulfur powder using Gewald synthesis ...technique and the intermediate was treated with 1,3-disubstituted pyrazole-4-carboxaldehyde to obtain the novel Schiff bases. 1,3-disubstituted pyrazole-4-carboxaldehyde derivatives have been synthesized by Vilsmeier-Haack reaction in the course of a multi-step reaction. The structure of novel compounds were established on the basis of their elemental analyses IR, 1H NMR, 13C NMR, and mass spectral data and then screened for their in vitro antimicrobial activity. Among them 5a, 5c, 5f and 5h showed excellent activity when compared to other derivatives. Remaining derivatives showed moderate activity.
A novel series of 1,2,3-triazole-linked pyrazoline analogues were prepared by the reaction of 3-(4-(benzyloxy)phenyl)-1-(1-(arylphenyl)-5-methyl-1
H
-1,2,3-triazol-4-yl)prop-2-en-1-one with hydrazine ...hydrate in the presence of glacial acetic acid medium. The structures of the newly synthesized pyrazoline derivatives were established by elemental analysis, FT-IR,
1
H NMR,
13
C{
1
H} NMR, and mass spectral analysis. In addition, synthesized compounds DFT calculations and 3D structures of the synthesized compounds were performed using Gaussian 09 software, hybrid models and MM2 force techniques were used to obtain energy minimized structures. The antibacterial activities of the synthesized pyrazolines were determined against Gram-positive and Gram-negative strains. Among them, compounds with
meta
-chloro substitution on phenyl ring of pyrazoline showed the highest magnitude of inhibition against
Pseudomonas aeruginosa
and bromo substitution on
para
position of phenyl ring exhibited highest magnitude of inhibition against
Staphylococcus aureus
.
Graphic abstract
5-methyl-2-(pyridin-3-yl)-1,3-thiazole-4-carbohydrazide (1) on treatment with 4-fluorobenzaldehyde in presence of catalytic amount of acetic acid, accessed the target compound (2) with the yield of ...79%. The target compound was confirmed by 1H-NMR, 13C-NMR, FT-IR and LCMS. In vitro antibacterial activity against Staphylococcus aureus (S. Aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa) were carried out and compound 2 showed promising activity against B. subtilis. In addition, compound 2 was analyzed for DNA binding study. It revealed that compound 2 has a promising affinity towards DNA double helix.
The Biginelli reaction has received significant consideration in recent years due to its easily accessible aldehyde, urea/thiourea, and active methylene compounds. When it comes to pharmacological ...applications, the Biginelli reaction end‐products, the 2‐oxo‐1,2,3,4‐tetrahydropyrimidines, are vital in pharmacological applications. Due to the ease of carrying out the Biginelli reaction, it offers a number of exciting prospects in various fields. Catalysts, however, play an essential role in Biginelli's reaction. In the absence of a catalyst, it is difficult to form products with a good yield. Many catalysts have been used in search of efficientmethodologies, including biocatalysts, Brønsted/Lewis acids, heterogeneous catalysts, organocatalysts, and so on. Nanocatalysts are currently being applied in the Biginelli reaction to improve the environmental profile as well as speed up the reaction process. This review describes the catalytic role in the Biginelli reaction and pharmacological application of 2‐oxo/thioxo‐1,2,3,4‐tetrahydropyrimidines. This study provides information that will facilitate the development of newer catalytic methods for the Biginelli reaction, by academics as well as industrialists. It also offers a broad scope for drug design strategies, which may enable the development of novel and highly effective bioactive molecules.
This review describes the catalytic role of 2‐oxo/thioxo‐1,2,3,4‐tetrahydropyrimidines in the Biginelli reaction and in pharmacological applications. The provided information will facilitate the development of newer catalytic methods for the Biginelli reaction, by academics and industrialists. The broad scope of drug design strategies may enable the development of novel and highly effective bioactive molecules.
•Coumarin-piperazine analogues were synthesized using the click chemistry approach.•Compounds were tested for anti-tubercular activity, compound 8d showed as the most promising.•Compound 8d also ...demonstrated significant inhibition of acetyl-CoA synthetase activity.•Anti-inflammatory potential was observed in compounds 8c, 8d, 8e, and 8j.•Strong antioxidant effects were noted in compounds 8c, 8d, 8i, and 8j.
In this study, a novel series of coumarin piperazine analogues were synthesized using Click chemistry approach. Thus synthesized compounds (8a-j) were evaluated for their pharmacological potentialities. These compounds subjected for evaluation of their anti-tubercular, anti-cancer, anti-inflammatory, and antioxidant properties. Results revealed that analogues 8b, 8d, 8i and 8h are found to be the promising drug-like candidates against Mycobacterium tuberculosis H37Rv strain exhibiting more potent activity than isoniazid with MIC of 2.24, 1.04, 3.72, 5.35 µM respectively. Furthermore, the compound 8d displayed better anti-inflammatory and antioxidant activity with IC50 values of 66.43 µM and 69.14 µM respectively. Molecular docking studies insights into the binding affinities and interactions with a target protein. The in silico ADME profiles supported their pharmacokinetic viability. Predominantly, compound 8d exhibited anticancer activity with IC50 values of 12.42 µM and 26.16 µM with reference to HeLa and MCF-7respectively by inhibiting acetyl-CoA synthetase. These findings highlight more specifically the compound 8d as a potent anti-cancer agent.
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•A new pyrimidine hybrids was synthesized with the help of WELPSA as an effective catalyst through a multicomponent one-pot Biginelli reaction.•Synthesized compounds were evaluated ...for α-amylase and α-glucosidase inhibition assays.•All the compounds were found remarkable with excellent IC50 values than the standard drug acarbose.•DFT calculations were performed using Gaussian 09 software.•Molecular docking study of the synthesized compounds was performed using Auto dock Vina.
A green catalyst WELPSA-catalyzed three-component condensation (Biginelli) process involving an aldehyde, barbituric/thiobarbituric/1,3-dimethylbarbituric acid, and urea/thiourea/guanidine hydrochloride in a single pot in presence of a green solvent for the production of DHPM have been presented. The catalyst is reusable and this methodology is scalable. By using the in vitro experiments, the antidiabetic potentiality of synthesized compounds that inhibit α-amylase along with α-glucosidase efficiencies was assessed. All the synthesized compounds except for 4a and 4e, showed the most significant inhibition for α-amylase and α-glucosidase activities. Among the synthesized DHPM compounds, 4c and 4b exhibited significant inhibition profiles compared to the standard antidiabetic drug acarbose. Furthermore, synthesized substances' energy-minimized structures, 3D structures, and DFT calculations were performed using Gaussian 09 software, hybrid models, and MM2 force approaches. Strong hydrogen bonds with amino acid residues Arg-672, Arg-600, Trp-613, Asp-404, Asp-282, and Asp-616 indicate that an α-glucosidase-inhibitory peptide may have hypoglycemic efficacy confirmed by the molecular docking study of the synthesized DHPM.
Herein, in this report we are introducing newly synthesized chalcone derivative, "(E)-1-phenyl-3-(4-((5-(((Z)-thiophen-2-ylmethylene)amino)-1,3,4-thiadiazol-2-yl)thio)phenyl)prop-2-en-1-one" (5), as ...a chemosensor to detect Fe2+ metal ions in HEPES buffer solution of pH 7.5. Spectroscopic techniques were used to confirm the synthesized sensor. To determine the chemical reactivity and molecular stability of the probe, a frontier molecular orbitals investigation was carried out. A molecular electrostatic potential map was investigated to know the binding site of 5 for metal ion coordination. The theoretical absorption and fluorescence emission properties were estimated and correlated with the experimental observations. The sensor showed excellent selectivity for Fe2+ compared to all other studied metal ions. The fluorescence binding studies were carried out by adding different amounts of Fe2+ ions for a fixed concentration of probe 5. The inclusion of Fe2+ ions resulted in a decrease in fluorescence intensity with a bathochromic shift of emission wavelength of 5 due to the 5-Fe2+ complexation. The binding affinity value for the probe was found to be 576.2 M-1 with the help of the Stern-Volmer plot. The Job's plot and mass spectra supported the 2:1 (5: Fe2+) stoichiometry of complex formation. The detection limit and limit of quantification of 5 for Fe2+ were calculated to be 4.79 × 10-5 M and 14.54 × 10-5 M. Further, in addition to this, the photophysical parameters such as fluorescence lifetime of 5 and 5-Fe2+ complex measured to be 0.1439 and 0.1574 ns. The quantum yield of 5 and 5-Fe2+ was found to be 0.0398 and 0.0376. All these experimental findings revealed that probe 5 has excellent selectivity and sensitivity for Fe2+ ions.
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