Interaction of the Anticancer Plant Alkaloid Sanguinarine with Bovine Serum Albumin

Maidul Hossain,Gopinatha Suresh Kumar,Asma Yasmeen Khan,Vladimir N Uversky

doi:10.1371/journal.pone.0018333

Maidul Hossain, Gopinatha Suresh Kumar + Show 2 more

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https://doi.org/10.1371/journal.pone.0018333

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Abstract

BackgroundInteraction of the iminium and alkanolamine forms of sanguinarine with bovine serum albumin (BSA) was characterized by spectroscopic and calorimetric techniques.Methodology/Principal FindingsFormation of strong complexes of BSA with both iminium and alkanolamine forms was revealed from fluorescence quenching of sanguinarine. Binding parameters calculated from Stern-Volmer quenching method revealed that the neutral alkanolamine had higher affinity to BSA compared to the charged iminium form. Specific binding distances of 3.37 and 2.38 nm between Trp 212 (donor) and iminium and alkanolamine forms (acceptor), respectively, were obtained from Forster resonance energy transfer studies. Competitive binding using the site markers warfarin and ibuprofen, having definite binding sites, demonstrated that both forms of sanguinarine bind to site I (subdomain IIA) on BSA. Sanguinarine binding alters protein conformation by reducing the α-helical organization and increasing the coiled structure, indicating a small but definitive partial unfolding of the protein. Thermodynamic parameters evaluated from isothermal titration calorimetry suggested that the binding was enthalpy driven for the iminium form but favoured by negative enthalpy and strong favourable entropy contributions for the alkanolamine form, revealing the involvement of different molecular forces in the complexation.Conclusions/SignificanceThe results suggest that the neutral alkanolamine form binds to the protein more favourably compared to the charged iminium, in stark contrast to the reported DNA binding preference of sanguinarine.

Highlights

Alkaloids are secondary metabolites of plants especially noteworthy for their remarkable biological activities and potential medicinal use
The binding parameters calculated from Stern-Volmer quenching method revealed that the affinity to bovine serum albumin (BSA) was higher for the neutral alkanolamine form compared to the charged iminium form
Specific distances of 3.37 and 2.38 nm, respectively, between Trp 212 and sanguinarine iminium and alkanolamine forms were obtained from Forster Resonance Energy transfer (FRET) studies

Summary

Introduction

Alkaloids are secondary metabolites of plants especially noteworthy for their remarkable biological activities and potential medicinal use. Sanguinarine (Figure 1), is a quaternary benzophenanthridine alkaloid, found in many botanical species [1]. It is a component of argemone oil, responsible for ‘epidemic dropsy’ [2]. Sanguinarine can exist as the cationic iminium (Figure 1A) and neutral alkanolamine (Figure 1B) forms with a pKa of 7.4 [17]. Effectiveness and efficacy of sanguinarine in therapeutic applications may be modified on the basis of its interaction with serum albumins that may be critical for understanding its toxicity and distribution in cells. Interaction of the iminium and alkanolamine forms of sanguinarine with bovine serum albumin (BSA) was characterized by spectroscopic and calorimetric techniques

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Conclusion