In silico and in vitro Study of the Inhibitory Effect of Antiinflammatory Drug Betamethasone on Two Lipases

Background: For the first time, the anti-inflammatory drug betamethasone is investigated for its inhibitory activity against lipase. Objective: This work aims to demonstrate the in vitro and in silico inhibitory effect of the anti-inflammatory drug betamethasone on the enzymatic activity of two lipases. Methods: In vitro study using p-nitrophenyllaurate as lipase substrate is used to determine inhibition potency. Molecular Docking is performed using the Autodock Vina for drug molecule and two enzymes Candida rugosa lipase and human pancreatic lipase. Results: Betamethasone represents a moderate inhibition effect with a value of IC50 of 0.36±0.01 mg/ml. Molecular docking allowed us to understand inhibitory – enzyme interactions and to confirm in vitro obtained results. Conclusion: These experiments showed that betamethasone can be used in the treatment of diseases related to lipase activity.

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The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies

The Natural Products Journal ◽

10.2174/2210315508666181009112415 ◽

2020 ◽

Vol 10 (3) ◽

pp. 208-215 ◽

Cited By ~ 1

Author(s):

Talia Serseg ◽

Khedidja Benarous ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Essential Oils ◽

In Silico ◽

Candida Rugosa ◽

Inhibitory Effect ◽

Mentha Piperita ◽

Inhibition Mechanism ◽

Syzygium Aromaticum ◽

In Silico Studies

Background: Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work. Objective: We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL. Methods: The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs. Results: We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules. Conclusion: These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.

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Synthesis and characterization of new inhibitors of cholinesterases based on N-phenylcarbamates: In vitro study of inhibitory effect, type of inhibition, lipophilicity and molecular docking

Bioorganic Chemistry ◽

10.1016/j.bioorg.2018.03.012 ◽

2018 ◽

Vol 78 ◽

pp. 280-289 ◽

Cited By ~ 2

Author(s):

Katarína Vorčáková ◽

Magdaléna Májeková ◽

Eva Horáková ◽

Pavel Drabina ◽

Miloš Sedlák ◽

...

Keyword(s):

Molecular Docking ◽

In Vitro Study ◽

Inhibitory Effect ◽

Vitro Study ◽

Synthesis And Characterization

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Cleroda-4(18),13-dien-15,16-olide as novel xanthine oxidase inhibitors: An integrated in silico and in vitro study

PLoS ONE ◽

10.1371/journal.pone.0253572 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253572

Author(s):

Ha Thi Nguyen ◽

Thien-Y Vu ◽

Tikam Chand Dakal ◽

Bhanupriya Dhabhai ◽

Xuan Hong Quan Nguyen ◽

...

Keyword(s):

Molecular Docking ◽

Xanthine Oxidase ◽

In Silico ◽

Hydrophobic Interactions ◽

Target Prediction ◽

Docking Simulation ◽

In Vitro Study ◽

Inhibitory Effect ◽

Reference Drug

In the present study, in silico predictions and molecular docking were performed on five clerodane diterpenes (1–5) from Polyalthia longifolia seeds to evaluate their potential as xanthine oxidase (XO) inhibitors. The initial screening was conducted by target prediction using TargetNet web server application and only compounds 3 and 4 showed a potential interaction with XO. Compounds 3 and 4 were subsequently subjected to in silico analyses on XO protein structure (PDB: 1N5X) using Schrödinger Release 2020–3 followed by structural modeling & molecular simulation studies to confirm the initial prediction result and identify the binding mode of these compounds to the XO. Molecular docking results revealed that compounds 3 (-37.3 kcal/mol) and 4 (-32.0 kcal/mol) binds more stably to XO than the reference drug allopurinol (-27.0 kcal/mol). Interestingly, two residues Glu 802 and Thr 1010 were observed as the two main H-bond binding sites for both tested compounds and the allopurinol. The center scaffold of allopurinol was positioned by some π-π stacking with Phe 914 and Phe 1009, while that of compounds 3 and 4 were supported by many hydrophobic interactions mainly with Leu 648, Phe 649, Phe 1013, and Leu 1014. Additionally, the docking simulation predicted that the inhibitory effect of compounds 3 and 4 was mediated by creating H-bond with particularly Glu 802, which is a key amino acid for XO enzyme inhibition. Altogether, in vitro studies showed that compounds 3 and 4 had better inhibitory capacity against XO enzyme with IC50 values significantly (p < 0.001) lower than that of allopurinol. In short, the present study identified cleroda-4(18),13-dien-15,16-olide as novel potential XO inhibitors, which can be potentially used for the treatment of gout.

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