Cytochrome P450 and P-gp Mediated Herb-Drug Interactions and Molecular Docking Studies of Garcinol

Garcinol is an active constituent of Garcinia indica and Garcinia cambogia. Recent studies have proven that garcinol has anti-inflammatory, anti-cancer, and anti-oxidant activities. The objective of this study was to evaluate the inhibitory effects of garcinol on the activities of the drug metabolizing cytochrome P450 (CYP) isozymes to predict potential herb-drug interactions with co-administered drugs. Garcinol was incubated with a mixture of rat liver microsomes and eight CYP probe substrate cocktail under optimized incubation conditions and the samples were analyzed using a validated method on LC-MS/MS. Garcinol showed strong inhibition with IC50 values of CYP1A2 (7.6 µM), CYP2C9 (8.0 µM), CYP2B6 (2.1 µM), CYP2D6 (9.5 µM), and CYP3A4 (5.1 µM), respectively, and moderate inhibition towards CYP2C19 (16.4 µM) and CYP2E1 (19.0 µM). Molecular docking studies were performed on garcinol against the active sites of CYP2B6 and CYP3A4 proteins. These results further confirmed that the inhibitory activity of garcinol occurred by occupying the active sites of these human CYPs and by making favorable interactions with its key residues. In-vivo CYP inhibition studies were carried out in Sprague-Dawley rats. These results suggest garcinol may cause herb-drug interactions, mediated by inhibition of CYPs involved in drug metabolism in-vivo by altering the pharmacokinetic parameters like AUC and Cmax in a clinically significant manner. Garcinol was found to upregulate the expression and activity of P-gp in western blotting study and P-gp inhibition study in-vivo. These findings give a clear understanding to predict potential herb-drug/drug-drug interactions of garcinol for safe clinical use in future.

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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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Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v13i2.35514 ◽

2018 ◽

Vol 13 (2) ◽

pp. 149 ◽

Cited By ~ 1

Author(s):

Naureen Shehzadi ◽

Khalid Hussain ◽

Nadeem Irfan Bukhari ◽

Muhammad Islam ◽

Muhammad Tanveer Khan ◽

...

Keyword(s):

Molecular Docking ◽

Video Clip ◽

Serum Levels ◽

Docking Studies ◽

Normal Serum ◽

Yeast Cells ◽

Drug Candidate ◽

Molecular Docking Studies

The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta2-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.Video Clip of Methodology:Glucose uptake by yeast cells: 4 min 51 sec <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a> <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a>

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A new class of potential antidiabetic acetohydrazides: Synthesis, in vivo antidiabetic activity and molecular docking studies

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v12i3.31428 ◽

2017 ◽

Vol 12 (3) ◽

pp. 319 ◽

Cited By ~ 1

Author(s):

Mubeen Arif ◽

Furukh Jabeen ◽

Aamer Saeed ◽

Irfan Zia Qureshi ◽

Nadia Mushtaq

Keyword(s):

Molecular Docking ◽

Video Clip ◽

Docking Studies ◽

Antidiabetic Activity ◽

Molecular Docking Studies ◽

H Nmr ◽

New Class ◽

Full Screen ◽

Pharmacologically Active

Two new pharmacologically active series of tetrazolopyridine-acetohydrazide conjugates [9 (a-n), 10 (a-n)] were synthesized by reacting a variety of suitably substituted benzaldehydes and isomeric 2-(5-(pyridin-3/4-yl)-2H-tetrazol-2-yl)acetohydrazides (7, 8). The synthesized compounds were analyzed through FTIR, 1H NMR, 13C NMR and elemental techniques. These acetohydrazides were screened for their in vivo antidiabetic activity and molecular docking studies. An excellent agreement was obtained as the best docked poses show-ed important binding features mostly based on interactions due to an oxygen atom and aromatic moieties of the series. The compounds 9a, 9c and 10l were found to be the most active in lowering blood glucose, having the potential of being good antidiabetic agents.Video Clip of Methodology:Synthesis of 3/4-(2H-tetrazole-5-yl)pyridine: 1 min 57 sec <a href="https://www.youtube.com/v/CHp8HxlEa2M">Full Screen</a> <a href="https://www.youtube.com/watch?v=CHp8HxlEa2M">Alternate</a>

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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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Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi

Food & Function ◽

10.1039/c5fo00519a ◽

2015 ◽

Vol 6 (8) ◽

pp. 2693-2700 ◽

Cited By ~ 27

Author(s):

Aditya Arvindekar ◽

Tanaji More ◽

Pavan V. Payghan ◽

Kirti Laddha ◽

Nanda Ghoshal ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Action ◽

Docking Studies ◽

Molecular Docking Studies ◽

Alpha Glucosidase

The 1,8-dihydroxyanthraquinones from the culinary and medicinally important plant Rheum emodi exert anti-hyperglycemic potential but notably different α-glucosidase actions as established by in vitro, in vivo, kinetics and molecular docking studies.

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Investigation of serum and brain superoxide dismutase levels depending on atomoxetine used in attention-deficit/hyperactivity disorder treatment: A combination of in vivo and molecular docking studies

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104435 ◽

2020 ◽

Vol 105 ◽

pp. 104435

Author(s):

Fatma Gür ◽

Bahri Gür ◽

Beyzagül Erkayman ◽

Zekai Halıcı ◽

Akar Karakoç

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Superoxide Dismutase ◽

Molecular Docking ◽

Attention Deficit ◽

Docking Studies ◽

Molecular Docking Studies ◽

Hyperactivity Disorder ◽

Disorder Treatment

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

Letters in Organic Chemistry ◽

10.2174/1570178615666180815124425 ◽

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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