Mechanochemical Synthesis, in vitro Evaluation and Molecular Docking Studies of 4-Amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles as Antidiabetic Agents

The synthesis of 4-amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles 4a-h, as example of 2,4-diaminothiazole-benzofuran hybrids and an evaluation of their antidiabetic activity, by in vitro and computational methods, are reported. The synthesis of these diaminothiazoles was achieved mechano chemically by a rapid solvent-less method. Their antidiabetic activity was assessed by α-glucosidase and α-amylase inhibition assays. The, IC50 value for α-glucosidase inhibition by 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) was found to be 20.04 µM and the IC50 value for α-amylase inhibition, 195.03 µM, whereas the corresponding values for reference acarbose were 53.38 µM and 502.03 µM, respectively. Molecular docking studies at the active sites of α- glucosidase and α-amylase showed that among the diaminothiazoles 4a-h now studied, 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) has the highest D-scores of -8.63 and -8.08 for α-glucosidase and for α-amylase, with binding energies -47.76 and -19.73 kcal/mol, respectively.

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Antioxidant, antimicrobial, and molecular docking studies of novel chalcones and Schiff bases bearing 1, 4-naphthoquinone moiety

Letters in Drug Design & Discovery ◽

10.2174/1570180819666211228091055 ◽

2021 ◽

Vol 19 ◽

Author(s):

Nadia Ali Ahmed Elkanzi ◽

Hajer Hrichi ◽

Rania B. Bakr

Keyword(s):

Molecular Docking ◽

Schiff Bases ◽

Active Sites ◽

Radical Scavenging ◽

Docking Studies ◽

Antimicrobial Compounds ◽

Molecular Docking Studies ◽

Fungal Strains ◽

Chemical Structures

Background: The 1,4-naphthoquinone ring has attracted prominent interest in the field of medicinal chemistry due to its potent pharmacological activity as antioxidant, antibacterial, antifungal, and anticancer. Objective: Herein, a series of new Schiff bases (4-6) and chalcones (8a-c & 9a-d) bearing 1,4-naphthoquinone moiety were synthesized in good yields and were subjected to in-vitro antimicrobial, antioxidant, and molecular docking testing. Methods: A facile protocol has been described in this study for the synthesis of new derivatives (4-7, 8a-c, and 9a-d) bearing 1,4-naphthoquinone moiety. The chemical structures of all the synthesized compounds were identified by 1H-NMR, 13C-NMR, MS, and elemental analyses. Moreover, these derivatives were assessed for their in-vitro antimicrobial activity against gram-positive, gram-negative bacteria, and fungal strains. Further studies were conducted to test their antioxidant activity using DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay. Molecular docking studies were realized to identify the most likely interactions of the novel compounds within the protein receptor. Results: The antimicrobial results showed that most of the compounds displayed good efficacy against both bacterial and fungal strains. The antioxidant study revealed that compounds 9d, 9a, 9b, 8c, and 6 exhibited the highest radical scavenging activity. Docking studies of the most active antimicrobial compounds within GLN- 6-P, recorded good scores with several binding interactions with the active sites. Conclusion: Based on the obtained results, it was found that compounds 8b, 9b, and 9c displayed the highest activity against both bacterial and fungal strains. The obtained findings from the DPPH radical scavenging method revealed that compounds 9d and 9a exhibited the strongest scavenging potential. The molecular docking studies proved that the most active antimicrobial compounds 8b, 9b and 9c displayed the highest energy binding scores within the glucosamine-6-phosphate synthase (GlcN-6-P) active site.

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Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22583 ◽

2020 ◽

Vol 32 (5) ◽

pp. 1151-1157 ◽

Cited By ~ 1

Author(s):

P. Raghurama Shetty ◽

G. Shivaraja ◽

G. Krishnaswamy ◽

K. Pruthviraj ◽

Vivek Chandra Mohan ◽

...

Keyword(s):

Antibacterial Activity ◽

Molecular Docking ◽

Anticancer Activity ◽

In Silico ◽

Active Sites ◽

Docking Studies ◽

Spectrometric Analysis ◽

Molecular Docking Studies ◽

In Vitro Investigation

In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

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α-Glucosidase Inhibition and Molecular Docking Studies of Natural Brominated Metabolites from Marine Macro Brown Alga Dictyopteris hoytii

Marine Drugs ◽

10.3390/md17120666 ◽

2019 ◽

Vol 17 (12) ◽

pp. 666 ◽

Cited By ~ 8

Author(s):

Najeeb Ur Rehman ◽

Kashif Rafiq ◽

Ajmal Khan ◽

Sobia Ahsan Halim ◽

Liaqat Ali ◽

...

Keyword(s):

Molecular Docking ◽

Brown Alga ◽

Docking Studies ◽

Spectroscopic Techniques ◽

Molecular Docking Studies ◽

Ethyl Methyl ◽

2D Noesy ◽

Ic50 Value ◽

Ic50 Values

Bioassay guided isolation of the methanolic extract of marine macro brown alga Dictyopteris hoytii afforded one new metabolite (ethyl methyl 2-bromobenzene 1,4-dioate, 1), one new natural metabolite (diethyl-2-bromobenzene 1,4-dioate, 2) along with six known metabolites (3–8) reported for the first time from this source. The structure elucidation of all these compounds was achieved by extensive spectroscopic techniques including 1D (1H and 13C) and 2D (NOESY, COSY, HMBC and HSQC) NMR and mass spectrometry and comparison of the spectral data of known compounds with those reported in literature. The in vitro α-glucosidase inhibition studies confirmed compound 7 to be the most active against α-glucosidase enzyme with IC50 value of 30.5 ± 0.41 μM. Compounds 2 and 3 demonstrated good inhibition with IC50 values of 234.2 ± 4.18 and 289.4 ± 4.91 μM, respectively, while compounds 1, 5, and 6 showed moderate to low inhibition. Furthermore, the molecular docking studies of the active compounds were performed to examine their mode of inhibition in the binding site of the α-glucosidase enzyme.

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Isolation of stigmasterol from hexane extract of leaves of Pisonia grandis R.Br, in vitro anti-diabetic and its molecular docking studies

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i2.2158 ◽

2020 ◽

Vol 11 (2) ◽

pp. 2117-2122

Author(s):

Abhijit Mitra ◽

Mohankumar Ramasamy ◽

Valentina Parthiban ◽

Thottempudi Ravi Teja ◽

Srikalyani Vemuri ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Hexane Extract ◽

Medicinal Uses ◽

Isolation And Purification ◽

Molecular Docking Studies ◽

Ic50 Value ◽

Isolated Compound ◽

Pisonia Grandis

Pisonia grandis R.Br belonging to the family Nyctaginaceae is a widely distributed evergreen tree in India known for its medicinal uses. The study was aimed to investigate the anti-diabetic property in the leaves of Pisonia grandis R.Br. The isolation and purification were performed by the conventional column chromatography and the resultant yield was found to be a white crystalline powder, which was further subjected for characterization through IR, 1H NMR, 13C NMR and Mass spectroscopy. From the characterization data, the isolated compound was identified as stigmasterol, it was first time isolated from the hexane extract of the leaves. The α-amylase inhibitory activity of stigmasterol from the hexane extract of the leaves of Pisonia grandis R.Br showed high potent activity with an IC50 value of 46μg/ml. The anti-diabetic activity of the compound against α-amylase and four other diabetic enzymes- α-glucosidase acid phosphatase, endo-β-N acetaglucosaminidase and β-glucuronidase were further investigated by molecular docking studies and proved that stigmasterol can be a potential anti-diabetic agent.

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Synthesis, biological evaluation and molecular docking studies of new 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonate derivatives on human aldose reductase enzyme

10.3762/bxiv.2021.31.v1 ◽

2021 ◽

Author(s):

Gül Özdemir ◽

Namık Kılınç ◽

Sevda Manap ◽

Murat Beytur ◽

Muzaffer Alkan ◽

...

Keyword(s):

Molecular Docking ◽

Antibacterial Activities ◽

Docking Studies ◽

Biological Evaluation ◽

Binding Energies ◽

Diffusion Method ◽

Alkyl Aryl ◽

Molecular Docking Studies ◽

New Compounds

A series of 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (3) were synthesized from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 2-ethoxy-4-formyl-phenyl benzenesulfonate (2). N-acetyl derivatives (4) of compounds 3 were also obtained. Then, the compounds 3 have been treated with morpholine and 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize 2-ethoxy-4-{[1-(morpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (5) and 2-ethoxy-4-{[1-(2,6-dimethylmorpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (6), respectively. The structures of twenty-six new compounds were identified by using elemental analysis, IR, 1H NMR, 13C NMR, and MS spectral data. In addition, in vitro antibacterial activities of the new compounds were evaluated against six bacteria such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klepsiella pneumonia according to agar well diffusion method. Furthermore, in order to determine the possible antidiabetic properties of the synthesized 1,2,4-triazole derivatives, inhibition effects on the AR enzyme were investigated and molecular docking studies were carried out to determine the receptor-ligand interactions of these compounds. IC50 values of triazole-derived compounds (6a, 6b, 6d-g) against AR enzyme were determined as 0.95 µM, 0.75 µM, 1.83 µM, 0.62 µM, 1.05 µM, 1.06 µM, respectively. Considering the docking scores and binding energies obtained docking studies, it has been shown that molecules fit very well to the active site of the AR enzyme.

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Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191105100959 ◽

2019 ◽

Vol 19 (29) ◽

pp. 2676-2686 ◽

Cited By ~ 1

Author(s):

Saddala Madhu Sudhana ◽

Pradeepkiran Jangampalli Adi

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Biological Evaluation ◽

Binding Energies ◽

Molecular Docking Studies ◽

Metal Chelating ◽

In Silico Admet ◽

Dpph Method

Aims: The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5- methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Background: An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine) 1 were chemical synthesized process. Materials & Methods: In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds 3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS method), cytotoxicity, molecular docking and in silico ADMET properties. Result: Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but 5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed the best binding energies and non-toxic properties. Conclusion: The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress associated diseases.

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Inhibitory Effect of Fisetin on α-Glucosidase Activity: Kinetic and Molecular Docking Studies

Molecules ◽

10.3390/molecules26175306 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5306

Author(s):

Beiyun Shen ◽

Xinchen Shangguan ◽

Zhongping Yin ◽

Shaofu Wu ◽

Qingfeng Zhang ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Competitive Inhibitor ◽

Inhibitory Effect ◽

Docking Studies ◽

Molecular Docking Studies ◽

Ic50 Value ◽

Cotinus Coggygria

The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be effective in alleviating hyperglycemia by inhibiting α-glucosidase. In this study, the α-glucosidase inhibitory activity of fisetin extracted from Cotinus coggygria Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC50 value of 4.099 × 10−4 mM. Enzyme kinetic analysis revealed that fisetin is a non-competitive inhibitor of α-glucosidase, with an inhibition constant value of 0.01065 ± 0.003255 mM. Moreover, fluorescence spectrometric measurements indicated the presence of only one binding site between fisetin and α-glucosidase, with a binding constant (lgKa) of 5.896 L·mol−1. Further molecular docking studies were performed to evaluate the interaction of fisetin with several residues close to the inactive site of α-glucosidase. These studies showed that the structure of the complex was maintained by Pi-Sigma and Pi-Pi stacked interactions. These findings illustrate that fisetin extracted from Cotinus coggygria Scop. is a promising therapeutic agent for the treatment of T2DM.

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