Integrated Approach to Interaction Studies of Pyrene Derivatives with Bovine Serum Albumin: Insights from Theory and Experiment

Abstract

This work aimed to investigate the interaction of bovine serum albumin with newly synthesized potent new pyrene derivatives (PS1 and PS2), which might prove useful to have a better antibacterial character as found for similar compounds in the previous report [ Bioconjugate Chemistry 2014 12 2269 2284 ]. However, to date, binding studies with plasma protein are still unknown. Steady-state fluorescence spectroscopy and lifetime fluorescence studies show that the static interaction binding mode and binding constants of PS1 and PS2 are 7.39 and 7.81 [ K b × 10 5 (M –1 )], respectively. The experimental results suggest that hydrophobic forces play a crucial role in interacting pyrene derivatives with BSA protein. To verify this, molecular docking and molecular dynamics simulations were performed to predict the nature of the interaction and the dynamic behavior of the two compounds in the BSA complex, PS1 and PS2, under physiological conditions of pH = 7.1. In addition, the free energies of binding for the BSA-PS1 and BSA-PS2 complexes were estimated at 300 K based on the molecular mechanics of the Poisson–Boltzmann surface (MMPBSA) with the Gromacs package. PS2 was found to have a higher binding affinity than PS1. To determine the behavior of the orbital transitions in the ground state geometry, we found that both compounds have similar orbital transitions from HOMO–LUMO via π → π* and HOMO–1–LUMO+1 via n → π*, which was included in the FMO analysis. A cytotoxicity study was performed to determine the toxicity of the compounds. Based on the MD study, the stability of the compounds with BSA and the dynamic binding modes were further revealed, as well as the nature of the binding force components involved and the important residues involved in the binding process. From the binding energy analysis, it can be assumed that PS2 may be more active than PS1.

Studies on the synthesis of sugar chalcone derivatives for protein binding

“…[3,4] Furthermore, incorporation of heterocyclic rings in the structural framework of chalcones will further increase their bioactivity. C-glycoside incorporated with chalcone which is said to be sugar chalcone hybrids [5] are expected to have wide applications in the field of medicine as drug. [6] Serum Albumins are one of the most abundant and soluble protein in blood plasma.…”

Design, synthesis, crystal structure, photophysical behavior and aggregation-induced emission of a novel pyrene scaffold multifunctional Schiff base ligand: inhibition of digestive enzymes and docking studies

“…26 Cathepsin B inhibitors are of considerable contemporary therapeutic significance. Pyrene based Schiff base ligands are well known for their antimicrobial, 27 chemosensing 28 and protein binding 29 aspects. However, pyrene based Schiff base ligands have not been employed previously as inhibitors of digestive enzymes.…”

Tracing the transition from covalent to non-covalent functionalization of pyrene through C-, N-, and O-based ionic and radical substrates using quantum mechanical calculations

“…[31][32][33][34][35] Interaction of different substrates with pyrene is also undertaken in several other studies highlighting the functionalization of pyrene or other pyrene-like model systems for a range of applications. [25][26][27]36,37 Recently, the interaction of pyrene with biomolecules and other systems have also been studied. Sengottiyan et al has reported the binding studies of plasma proteins pyrene derivatives addressing the antimicrobial resistance.…”

“…Sengottiyan et al has reported the binding studies of plasma proteins pyrene derivatives addressing the antimicrobial resistance. 36 Another study reports the role of pyrene in probing different protein conformations thereby highlighting its importance in molecular organization of biological molecules 37 and in elucidating how mechanochromic luminescence behaviours can be modulated by side-chain substituents. 38 Several studies have reported pyrene as a model system for studying the properties of graphene for various applications, viz., eld effect transistors, hydrogen chemisorption, reactions in interstellar medium, etc.…”

“…31–35 Interaction of different substrates with pyrene is also undertaken in several other studies highlighting the functionalization of pyrene or other pyrene-like model systems for a range of applications. 25–27,36,37…”