scholarly journals Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1511 ◽  
Author(s):  
Danish Shahzad ◽  
Aamer Saeed ◽  
Fayaz Ali Larik ◽  
Pervaiz Ali Channar ◽  
Qamar Abbas ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antioxidant Activities ◽  
Competitive Inhibitor ◽  
Docking Studies ◽  
Design Synthesis ◽  
Kinetic Evaluation ◽  
Ic50 Value ◽  
Amylase Inhibitors ◽  
Burk Plot

A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a–5h, have been synthesized, characterized by 1H-NMR and 13C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC50 = 6.109 ± 0.329 µM), and the IC50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC50 = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results

Design, Synthesis, Molecular Docking Study and Anti-Hepatocellular Carcinoma Evaluation of New Bis-Triazolothiadiazines

2020 ◽  
Vol 20 (9) ◽  
pp. 788-800 ◽  
Author(s):  
Sobhi M. Gomha ◽  
Zeinab A. Muhammad ◽  
Elham Ezz El-Arab ◽  
Amira M. Elmetwally ◽  
Abdelaziz A. El-Sayed ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Reference Drug ◽  
Ic50 Value

Objective: The reaction of bis(4-amino-4H-1,2,4-triazole-3-thiol) with hydrazonoyl halides and α-halo-ketones gave a new series of bis-1,2,4-triazolo[3,4-b]thiadiazine derivatives. Methods: The structure of the new products was established on the basis of their elemental and spectral data (mass, 1H NMR, 13C NMR and IR) and an alternate method. Results: Several of the synthesized products were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HepG-2) and the results showed that compounds 16, 14 and 12 have promising activities (IC50 value of 24.8±9.1, 28.3±0.5, and 31±2.9μM, respectively) compared with Harmine reference drug (IC50 value of 22.4±1.11 μM). Conclusion: Moreover, molecular docking studies were performed to analyze the binding modes of the discovered hits into the active site of DYRK1A using iGEMDOCK.

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

Molecules ◽  
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.

scholarly journals Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

2020 ◽  
Vol 21 (24) ◽  
pp. 9623
Author(s):  
Łukasz Szczukowski ◽  
Edward Krzyżak ◽  
Adrianna Zborowska ◽  
Patrycja Zając ◽  
Katarzyna Potyrak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Biological Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Dna Strand ◽  
Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

Design, synthesis, in-vitro evaluation and molecular docking studies of novel indole derivatives as inhibitors of SIRT1 and SIRT2

2019 ◽  
Vol 92 ◽  
pp. 103281 ◽  
Author(s):  
Ramu Manjula ◽  
Nikhila Gokhale ◽  
Sruthi Unni ◽  
Prashant Deshmukh ◽  
Rajkumar Reddyrajula ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Indole Derivatives ◽  
Design Synthesis ◽  
In Vitro Evaluation ◽  
Molecular Docking Studies

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

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 666 ◽  
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.

scholarly journals Synthesis, Urease Inhibition, Antioxidant, Antibacterial, and Molecular Docking Studies of 1,3,4-Oxadiazole Derivatives

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Muhammad Hanif ◽  
Khurram Shoaib ◽  
Muhammad Saleem ◽  
Nasim Hasan Rama ◽  
Sumera Zaib ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Potassium Hydroxide ◽  
Antioxidant Activities ◽  
Docking Studies ◽  
Potassium Salts ◽  
Jack Bean ◽  
Molecular Docking Studies ◽  
Oxadiazole Derivatives ◽  
Urease Inhibitory

A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results.

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

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.

Computational Druglikeness Assessment, Synthesis, Characterization and in vitro Biological Activity Evaluation of some Novel Mixed Metal Complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide

2020 ◽  
Vol 23 ◽  
Author(s):  
Tahmeena Khan ◽  
Iqbal Azad ◽  
Alfred J. Lawrence ◽  
Saman Raza ◽  
Seema Joshi ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Docking Studies ◽  
Mixed Metal ◽  
Ic50 Value ◽  
Mixed Metal Complexes ◽  
Mcf 7

Aims and Objectives: The heteronuclear (mixed metal) complexes of Schiff bases have been explored as part of the coordination and bioinorganic chemistry. Five novel mixed metal complexes of (E)-2-(butan-2-ylidene) hydrazinecarbothioamide (2-butanone thiosemicarbazone) were prepared and characterized by different spectroscopic techniques. Molecular docking studies were performed with three proteins for two complexes. The toxicity potential, physicochemical properties and bioactivity scores were also predicted. The complexes were tested against three cell lines and also evaluated for their antibacterial activity. Materials and Methods: The mixed metal complexes were prepared in 1:4 molar ratio of metal salt and ligand. OSIRIS 4.6.1 was used to assess the toxicity whereas Molinspiration 2016.03 was used to calculate the bioactivity scores and other physicochemical properties. Principal Component Analysis (PCA) was performed using the Osiris Property Explorer 4.5.1 for defining and visualizing multidimensional property spaces by assigning dimensions to numerical descriptors. Molecular docking studies were performed with three proteins. The anticancer activity was tested against MCF-7, MDA-MB-231, HepG2 and A549 cell lines using MTT assay whereas antibacterial activity was tested using disc diffusion method. Results and Conclusion: The melting points of the complexes were as high as >3500C, indicating high thermal stability. [CuZn(C5H11N3S)4(SO4)2] exhibited minimum energies against the selected proteins. The bioactivity scores of the complexes were between -0.50 and 0.0. All the prepared complexes showed negative Ames score predicted their non-carcinogenic nature. Against A549 [CuZn(C5H11N3S)4(SO4)2], [CoZn(C5H11N3S)4(SO4)Cl2] and [FeZn(C5H11N3S)4(SO4)2] showed potential in vitro activity. IC50 of these three complexes were 19.69, 37.73 and 38.4 respectively. Against MCF-7, [FeCu(C5H11N3S)4(SO4)2] had IC50 value 53.5. Whereas, against HepG2 [CoZn(C5H11N3S)4(SO4)Cl2] was active having IC50 value 61.8. [CoZn(C5H11N3S)4(SO4)Cl2], [FeCu(C5H11N3S)4(SO4)2] and [FeCo(C5H11N3S)4(SO4)Cl2] were active against S. aureus in the concentration range 2-20 mg/mL. The complexes showed improved biological activity as compared to the monometallic complexes of the same ligand.

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

2019 ◽  
Vol 16 (7) ◽  
pp. 560-568
Author(s):  
Vijayan R. Akhila ◽  
Maheswari R. Priya ◽  
Daisy R. Sherin ◽  
Girija K. Krishnapriya ◽  
Sreerekha V. Keerthi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Mechanochemical Synthesis ◽  
Active Sites ◽  
Docking Studies ◽  
Binding Energies ◽  
Antidiabetic Activity ◽  
Antidiabetic Agents ◽  
Molecular Docking Studies ◽  
Ic50 Value

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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