Elucidating the binding interaction of andrographolide with the plasma proteins: biophysical and computational approach

Yeggoni, Daniel Pushparaju; Kranjec, Christian; Rachamallu, Aparna; Subramanyam, Rajagopal

doi:10.1039/c6ra25671f

Cited by 36 publications

(21 citation statements)

References 55 publications

(65 reference statements)

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“…The results were shown in ( Fig 7A–7L ), and are generated by using the Pymol software ( https://pymol.org ), and Ligplot ( www.ebi.ac.uk/thornton-srv/software/LIGPLOT ) is used to illustrate the two-dimensional interaction by hydrogen bond formation and hydrophobic interactions. The Binding constant values calculated computationally were in accordance with the values obtained experimentally [ 31 , 39 ].…”

Section: Resultssupporting

confidence: 82%

“…Using site specific markers we can understand the exact binding of ligand molecules to the specific domains of HSA. Hence, there are different site specific markers like lidocaine for domain I, phenylbutazone for domain II and ibuprofen for domain III [ 22 ] and using these markers the fluorescence was performed to analyze the specific binding domain of HSA on interaction with withanoside and withanolide derivatives [ 28 , 31 ]. Because of the structural and molecular similarity of four derivatives, all of them showed fluorescence emission quenching by displacing phenylbutazone, i.e.…”

Section: Resultsmentioning

confidence: 99%

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Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

et al. 2018

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Withania somnifera (Ashwagandha) is an efficient medicinal plant known in Ayurveda and Chinese medicine since ancient times, whose extracts are consumed orally as food supplement or as a health tonic owing to its several restorative properties for various CNS disorders, inflammation, tumour, stress, rheumatism etc. In this study, we have analyzed the binding interaction of four derivatives of Withania somnifera (Withanolide A, Withanolide B, Withanoside IV and Withanoside V) with HSA because of their important pharmacological properties. To unravel the binding between derivatives of Withania somnifera and HSA, fluorescence spectroscopy was used. Binding studies were further studied by molecular docking and dynamics and results confirmed greater stability upon binding of derivatives with HSA. Circular dichroism data illustrated change in the secondary structure of protein upon interaction with these derivatives, particularly the helical structure was increased and β-sheets and random coils were decreased. Furthermore, morphological and topological changes were observed using AFM and TEM upon binding of ligands with HSA indicating that HSA-withnoside/withanolide complexes were formed. All the results cumulatively demonstrate strong binding of withanosides and withanolides derivatives with serum albumin, which should further be explored to study the pharmacokinetics and pharmacodynamics of these derivatives.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

et al. 2018

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“…were shown in (Fig 6A-L), and are generated by using the Pymol software, and Ligplot is used to illustrate the two-dimensional interaction by hydrogen bond formation and hydrophobic interactions. The Binding constant values calculated computationally were in accordance with the values obtained experimentally [32,40].…”

Section: Molecular Dockingsupporting

confidence: 84%

“…Using site specific markers we can understand the exact binding of ligand molecules to the specific domains of HSA. Hence, there are different site specific markers like lidocaine for domain I, phenylbutazone for domain II and ibuprofen for domain III [22] and using these markers the fluorescence was performed to analyze the specific binding domain of HSA on interaction with withanoside and withanolide derivatives [28,32]. Kcal M -1 respectively (Fig 2 A-D).…”

Section: Displacement Studiesmentioning

confidence: 99%

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

Dubey

Kallubai

Sarkar

et al. 2018

Preprint

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Withania somnifera (Ashwagandha) is an efficient plant known in Ayurveda and Chinese medicine since ancient times, whose extracts are consumed orally as food supplement or as a health tonic owing to its several restorative properties for various CNS disorders, inflammation, tumour, stress and rheumatism. In this study, we have analyzed the binding interaction of four derivatives of Withania somnifera (Withanolide A, Withanolide B, Withanoside IV and Withanoside V) with HSA because of their important pharmacological properties. To unravel the binding between derivatives of Withania somnifera and HSA,fluorescence spectroscopy was used .Binding studies were further studied by molecular docking and dynamics studies and results confirmed greater stability upon binding of derivatives with HSA. Circular dichroism data illustrated change in the secondary structure of protein upon interaction with these derivatives, particularly the helical structure was increased and β-sheets and random coils were decreased .Furthermore, morphological and topological changes were observed using AFM and TEM upon binding of ligands with HSA indicating that HSA-withnoside/withanolide complexes were formed. All the results cumulatively demonstrate strong binding of withanosides and withanolides derivatives with serum albumin, which should further be explored to study the pharmacokinetics and pharmacodynamics of these derivatives.

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“…9,10 This protein plays an important role in the transport, absorption, distribution, and metabolism of drugs in the body. 11,12 Crystallographic analyses have revealed that HSA is a 585-residue protein composed of three domains (I-III). Two subdomains (A and B) comprise an intact domain.…”

Section: Introductionmentioning

confidence: 99%

Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

et al. 2018

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Trametinib is a novel anticancer drug for treating metastatic cutaneous melanoma. The present study probed into the binding of trametinib to human serum albumin (HSA) through spectroscopy methods and molecular simulations. Trametinib could quench the fluorescence of HSA through static quenching which could be probed via fluorescence spectroscopy and time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrogen bonds and van der Waals forces play crucial roles in this binding process, which exerts almost no effect on the HSA conformation under synchronous fluorescence, three-dimensional fluorescence, circular dichroism spectra, and molecular dynamics simulations. Site marker displacement experiments and molecular docking reveal that trametinib primarily binds to Sudlow site I of HSA. In addition, the trametinib-HSA interaction was hardly influenced by varying amino acid (glutamine, alanine, glycine, and valine) concentrations. This study can provide useful information for the pharmacokinetic properties of trametinib.

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Elucidating the binding interaction of andrographolide with the plasma proteins: biophysical and computational approach

Abstract: A phytochemical andrographolide is an anticancer agent with a stable conformation that strongly binds to the plasma proteins.

Cited by 36 publications

References 55 publications

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

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