Interaction between the Antimalarial Drug Dispiro-Tetraoxanes and Human Serum Albumin: A Combined Study with Spectroscopic Methods and Computational Studies

Abstract

Dispiro-tetraoxanes, a class of fully synthetic peroxides which can be used as an antiplasmodial remedy for multiple drug-resistant strains of Plasmodium falciparum, were selected for the interaction study with human serum albumin (HSA). The insight into the interaction of the two chemically synthesized, most potent antimalarial tetraoxane analogues (TO1 and TO2) and HSA has been scrutinized using distinct spectroscopic techniques such as. UV–visible absorption, fluorescence, time-resolved fluorescence, and circular dichroism (CD). Fluorescence quenching experiments divulged the static mode of quenching and binding constants obtained (∼104) indicated the moderate affinity of the analogues to HSA. CD confirmed the conformational changes in the serum albumin upon interaction with these analogues. Molecular docking validated the empirical results as these two analogues bind through hydrophobic interactions and hydrogen bonding with HSA. Present work first defined the binding mechanism of dispiro-tetraoxanes with HSA and thus provides a fresh insight into the drug transportation and metabolism. The present study could direct toward designing more potent tetraoxane analogues for their use in the biomedical field.

Effect of a Metal Ion in Modulating the Binding Interaction of a Dietary Flavonoid with Bovine Serum Albumin and DNA: A Spectroscopic and Theoretical Approach

“…CD is a sensitive and reliable technique to observe the secondary structure conformational changes in BSA upon the interaction with a ligand. Figure shows that the CD spectrum of native BSA displays two characteristic negative minima at ∼208 and ∼222 nm owing to the π–π* and n –π* transitions of the α-helix and random coil of BSA, respectively. , Interestingly, a continuous shift of the band at 208 nm toward 222 nm was observed. This shift of the spectral position arises due to the binding of the rutin–Fe­(II) complex with amino acid residues of the main polypeptide sequence of BSA and affects its hydrogen bond interaction. , Additionally, successive addition of the rutin–Fe­(II) complex to BSA decreased the band intensity, indicating a loss in the α-helical content in BSA.…”

“…Figure 6 shows that the CD spectrum of native BSA displays two characteristic negative minima at ∼208 and ∼222 nm owing to the π−π* and n−π* transitions of the α-helix and random coil of BSA, respectively. 53,54 Interestingly, a continuous shift of the band at 208 nm toward 222 nm was observed. This shift of the spectral position arises due to the binding of the rutin−Fe(II) complex with amino acid residues of the main polypeptide sequence of BSA and affects its hydrogen bond interaction.…”

Prediction of Deleterious nsSNPs Causing CHARGE Syndrome Associated with the CHD7 Protein using Computational Approaches

“…The superimposed structural investigation was completed for a native and mutant amino acid with PyMOL software. 39 The superimposed structures of P2683S and R2702C nsSNPs. In both the images, green color stick model represents the native amino acid, and the blue color represents the substituted Deleterious amino acid.…”

Multispectroscopic Studies on HSA Interaction, DFT Calculations, Molecular Docking, and Antimicrobial Activities of Imine‐ Functionalized Tris(hydroxymethyl)aminomethane Derivatives

“…Moreover, this complexation reduces the distribution of a drug in the tissues and may prevent it from reaching the biological target. [29] Therefore, understanding the mechanism of a drug's interaction with serum albumin is essential in knowing how the drug is transported and distributed throughout the body. Additionally, it will offer theoretical guidance and important information for developing more effective pharmaceuticals.…”

“…In protein‐drug interaction during binding, the drug is clasped in the plasma by HSA, which also limits the drug‘s clearance, lengthening pharmacokinetic half‐life. Moreover, this complexation reduces the distribution of a drug in the tissues and may prevent it from reaching the biological target [29] . Therefore, understanding the mechanism of a drug‘s interaction with serum albumin is essential in knowing how the drug is transported and distributed throughout the body.…”