The importance of intramolecular hydrogen bonds on the translocation of the small drug piracetam through a lipid bilayer

Coimbra, João T. S.; Feghali, Ralph; Ribeiro, Rui P.P.L.; Ramos, María J.; Fernandes, Pedro A.

doi:10.1039/d0ra09995c

Cited by 61 publications

(40 citation statements)

References 76 publications

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“…As far as the chemically synthesized derivatives are concerned, they display moderate to low solubility. Hydrogen bond donors and acceptors can contribute to the solubility and binding to the desired targets, but the presence of too many of such groups negatively impacts the permeability through cell membranes [ 114 ]. The derivatives tested possess an adequate amount of hydrogen bond donors and acceptors, aside from FA sugar derivatives, in which a high number of such groups is observed.…”

Section: Resultsmentioning

confidence: 99%

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

2022

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The main protease (Mpro) of SARS-CoV-2 is an appealing target for the development of antiviral compounds, due to its critical role in the viral life cycle and its high conservation among different coronaviruses and the continuously emerging mutants of SARS-CoV-2. Ferulic acid (FA) is a phytochemical with several health benefits that is abundant in plant biomass and has been used as a basis for the enzymatic or chemical synthesis of derivatives with improved properties, including antiviral activity against a range of viruses. This study tested 54 reported FA derivatives for their inhibitory potential against Mpro by in silico simulations. Molecular docking was performed using Autodock Vina, resulting in comparable or better binding affinities for 14 compounds compared to the known inhibitors N3 and GC376. ADMET analysis showed limited bioavailability but significantly improved the solubility for the enzymatically synthesized hits while better bioavailability and druglikeness properties but higher toxicity were observed for the chemically synthesized ones. MD simulations confirmed the stability of the complexes of the most promising compounds with Mpro, highlighting FA rutinoside and compound e27 as the best candidates from each derivative category.

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Section: Resultsmentioning

confidence: 99%

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

2022

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“…The extensively intramolecularly H-bonded conformations of CsA observed in nonpolar solvents would be expected to be more lipophilic than those with more exposed polar surface area and to have lower dehydration free energy penalties when they are transferred from aqueous to nonpolar environments (see, e.g., refs − and the review by Whitty et al).…”

Section: Overview Of Cyclosporin Structure and Permeabilitymentioning

confidence: 99%

Cyclosporin Structure and Permeability: From A to Z and Beyond

et al. 2021

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Cyclosporins are natural or synthetic undecapeptides with a wide range of actual and potential pharmaceutical applications. Several members of the cyclosporin compound family have remarkably high passive membrane permeabilities that are not well-described by simple structural metrics. Here we review experimental studies of cyclosporin structure and permeability, including cyclosporin–metal complexes. We also discuss models for the conformation-dependent permeability of cyclosporins and similar compounds. Finally, we identify current knowledge gaps in the literature and provide recommendations regarding future avenues of exploration.

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“…In the drug-receptor study, the hydrogen bond is also interesting to be investigated because hydrogen bonds are suggested to play a crucial role in facilitating the protein-ligand binding that affects molecular recognition, structural stability, protein activity, and compound permeability. Moreover, several simultaneous hydrogen bonds are suggested to increase the strength and stability of ligand-protein interaction [18,34]. Therefore, the hydrogen bonds between astaxanthin and phycocyanobilin to the investigated pro-inflammatory proteins may result in better stability interaction that provides higher immunomodulatory potency.…”

Section: The Potency Of Microalgae Pigments For Treating Covid-19mentioning

confidence: 99%

Microalgae pigments as a promising immunomodulating food ingredient: In silico study

Widyaningrum

Oktafika

Cecilia

2022

IOP Conf. Ser.: Earth Environ. Sci.

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Microalgae pigments attract the commercial market as functional food ingredients because of their potential as an antioxidant and anti-inflammatory agents. Through in vitro and in vivo studies, microalgae pigments showed a potential therapeutic effect to reduce the expression of pro-inflammatory cytokines by inhibiting inflammation signaling. Our study explored the potency of microalgae pigments as an immunomodulator by modeling the direct interaction between pigments and pro-inflammatory proteins by molecular docking. The docking study was carried out using AutoDock Vina. At the same time, the binding visualization was obtained by using Discovery Studio Visualizer. The result showed all investigated microalgae pigments (i.e., phycocyanobilin, astaxanthin, β-carotene, 9-cis- (β-carotene, and violaxanthin) docked to pro-inflammatory proteins (i.e., IL-6, TNF-α, and NIK), respectively in various binding energy. The binding between pigment compounds and the target protein is mostly attributed to the Van der Waals interaction. Notably, the pigments docked in crucial residues in proinflammatory proteins, suggesting the effect of the protein interaction on its receptor and cytokines activity. The results showed a therapeutic potency of microalgae pigment to support immune system modulation that could prevent and attenuate chronic inflammation.

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The importance of intramolecular hydrogen bonds on the translocation of the small drug piracetam through a lipid bilayer

Abstract: Using computational strategies and an analogue compound, we explore and measure the impact of intramolecular hydrogen bonds on the translocation of the small drug piracetam, through biological membrane models.

Cited by 61 publications

References 76 publications

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

Cyclosporin Structure and Permeability: From A to Z and Beyond

Microalgae pigments as a promising immunomodulating food ingredient: In silico study

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