Exploring the binding dynamics of etoricoxib with human hemoglobin: A spectroscopic, calorimetric, and molecular modeling approach

Abstract

Etoricoxib, widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and related conditions has ample affinity to bind with globular proteins. Here, the molecular interaction between purified human hemoglobin (HHb), a major heme protein and etoricoxib, a cyclooxygenase-2 inhibitor was studied by various spectroscopic, calorimetric, and molecular modeling techniques. The binding affected hypochromic changes in the Soret band of hemoglobin (Hb) and induced remarkable quenching of the intrinsic fluorescence property of protein molecules. Synchronous fluorescence studies revealed alterations in tryptophan (Trp) and tyrosine (Tyr) microenvironments of HHb molecule in presence of etoricoxib. Flouremetric and isothermal titration calorimetric studies suggested two binding sites in HHb for etoricoxib at three different temperatures (298.15, 303.15, and 310.15 K). Negative values of Gibbs energy change (ΔG) and enthalpy change (ΔH) strongly suggest that it is spontaneous and exothermic reaction, mainly stabilized by hydrogen bonding as evidenced by sucrose binding assay. These findings support our in silico molecular docking study, which specified the binding site and the non-covalent interactions involved in the association. Moreover, the interaction impacts on structural integrity and functional aspects of HHb as confirmed by decreased α helicity, increased free iron release, increased rate of co-oxidation, and decreased rate of esterase activity. Overall, these studies conclude that etoricoxib leads to a remarkable alteration in the conformational aspects of binding to HHb. Communicated by Ramaswamy H. Sarma.

An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2

“…Besides, the positive value of ∆S suggested that binding between compound SC2 and COX2 was mainly hydrophobic-force-driven, which was also shown in COX2-YB2 systems. A negative ∆H value was usually seen as proof for hydrogen bonds in the binding process [45,46]. This part corroborated the existence of hydrogen bonding in all three compound-COX2 systems, which agreed with the docking results.…”

Interactions of Gallic Acid with Porcine Hemoglobin: Effect on the Redox State and Structure of Hemoglobin

“…UV–vis absorption spectroscopy is a useful method to explore protein structure change induced by some small molecules . The UV–vis absorption spectra of Hb in the absence and presence of GA were collected (pH 7.4, 25 °C).…”

“…UV−vis absorption spectroscopy is a useful method to explore protein structure change induced by some small molecules. 31 The UV−vis absorption spectra of Hb in the absence and presence of GA were collected (pH 7.4, 25 °C). As shown in Figure 2A, native Hb exhibited characteristic peaks at 414 nm, which corresponded to the porphyrin Soret band, 271 nm because of the aromatic amino acid residues (Trp and Tyr), and 343 nm representing the ε-band and peaks over the 500−650 nm range are characteristics of the oxy-band or Q band.…”