Interaction of acridinedione dye with a globular protein in the presence of site selective and site specific binding drugs: Photophysical techniques assisted by molecular docking methods

Photophysical investigations and molecular docking studies of photoinduced electron transfer (PET) based fluorophores of acridine family with a globular protein, Bovine Serum Albumin (BSA) bound to non-narcotic drugs like phenylbutazone (PB) and flufenamic acid (FA) were carried out in aqueous solution. PB and FA are site specific and site selective drugs, wherein PB predominantly binds at the site (I) whereas FA selectively orients towards site (II) of BSA. Acridinedione (AD) dyes, both resorcinol and dimedone based are hydrophobic in nature and exhibits a combination of both hydrophobic and hydrogen-bonding interactions that are based on the binding sites in BSA. The extent of displacement of AD from the binding sites of BSA by PB and FA are elucidated and established from variation in the fluorescence lifetime and relative amplitude distribution of free and dye bound in site (I) and site (II). The extent of binding affinity of PB-BSA and FA-BSA in the presence of AD is minimal when compared to other site I and II drugs. This is attributed to AD dye bound to several amino acid residues present in BSA such that the dye prefers multiple binding sites in BSA even in the presence of FA and PB. Further, the dye bound to several amino acid residues of BSA ascertains the combination of hydrogen-bonding, hydrophobic interactions, pi-pi and pi-alkyl interaction apart from the binding through sites (I) and (II) from molecular docking methods. The combination of fluorescence tools with molecular modelling techniques provides an excellent approach in determining the stability of these complexes containing competitive guest molecules in the presence of a fluorescence probe and the binding characteristics of dye in a micro heterogeneous environment. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study investigates the photophysical properties and molecular docking interactions of acridine-based fluorophores with Bovine Serum Albumin (BSA) and non-narcotic drugs phenylbutazone (PB) and flufenamic acid (FA) in aqueous solution. It reveals that PB and FA displace the acridinedione (AD) dyes from specific binding sites in BSA, while the dyes prefer multiple binding sites in the presence of FA and PB. The combination of fluorescence tools with molecular modeling techniques is effective in determining the stability and binding characteristics of these complexes in a micro heterogeneous environment.