Biomolecular interaction mechanism of an anticancer drug, pazopanib with human serum albumin: a multi-spectroscopic and computational approach

Kandandapani, Salanee; Kabir, Md. Zahirul; Ridzwan, Nor Farrah Wahidah; Mohamad, Saharuddin Bin; Tayyab, Saad

doi:10.1080/07391102.2021.1911850

Cited by 4 publications

(2 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The HSA–MUB binding strengths ( K b = 1.48 × 10 4 M –1 ) have been not significantly affected by the DASA ( K b = 1.41 ± 0.03 × 10 4 M –1 ) and PAZO ( K b = 1.47 ± 0.05 × 10 4 M –1 ) presence, which implies that the simultaneous MUB administration with DASA or PAZO may not affect the transport of these drugs by HSA under in vitro physiological conditions. MUB, DASA, and PAZO are predicted to bind to the same HSA binding site (site I), , so the expected behavior for competition experiments with ternary mixture would be drug displacement and consequently a reduction of K b values. However, the presence of simultaneous drug interactions at the binding site I is possible, given the existence of a subsite that allows the coexistence of drugs in this common location .…”

Section: Resultsmentioning

confidence: 99%

Molecular Recognition Study toward the Mitochondrial Electron Transport Chain Inhibitor Mubritinib and Human Serum Albumin

2023

View full text Add to dashboard Cite

The ability to bind plasma proteins helps in comprehending relevant aspects related to the pharmacological properties of many drugs. Despite the vital role of the drug mubritinib (MUB) in the prophylaxis of various diseases, its interaction with carrier proteins still needs to be clarified. The present work focuses on the interaction between MUB and Human serum albumin (HSA), investigated by employing multispectroscopic, biochemical, and molecular docking approaches. The results reveal that MUB has quenched HSA intrinsic fluorescence (following a static mechanism) by attaching very close (r = 6.76 Å) and with moderate affinity (K b ≈ 104 M–1) to the protein site I (mainly by H-bonds, hydrophobic and Van der Waals forces). On one side, the HSA–MUB interaction has been accompanied by a slight disturbance in the HSA chemical environment (around the Trp residue) and protein secondary structure modifications. On another side, MUB competitively inhibits HSA esterase-like activity, which is very similar to other Tyrosine kinase inhibitors, and evidence that protein functional alterations have been triggered by MUB interaction. In summary, all of the presented observations can shed light on diverse pharmacological factors associated with drug administration.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular Recognition Study toward the Mitochondrial Electron Transport Chain Inhibitor Mubritinib and Human Serum Albumin

2023

View full text Add to dashboard Cite

show abstract

“…Numerous therapeutic drugs have been shown to bind proteins with intermediate binding affinity. [40][41][42][43][44] Furthermore, a decline in the Ka value with rising temperature suggested destabilization of the REG-protein complex with increasing temperature [45][46][47] Quantitative evaluation of the energetics of ligandprotein interaction is crucial as it provides valuable information regarding binding forces such as hydrogen bonds, electrostatic, hydrophobic and van der walls forces. [48] Analysis of the temperature dependence of the Ka values using Eq.…”

Section: Binding Characteristics and Thermodynamics Of The Reg-hsa Sy...mentioning

confidence: 99%

Molecular Recognition between Anticancer Drug, Regorafenib and Human Serum Albumin: Interaction Revisited

et al. 2022

View full text Add to dashboard Cite

The wet-lab techniques (fluorimetry and spectrophotometry), along with computational techniques (molecular docking and molecular dynamics (MD) simulation), were applied to re-examine the association of an anticancer drug, regorafenib (REG) with human serum albumin (HSA). The REG-induced protein fluorescence quenching was characterized as static quenching based on a decrement in the KSV (Stern-Volmer constant) with increasing temperature and hyperchromic effect in the absorption spectra. The REG-HSA complex (Ka = 0.63 -1.17 × 10 5 M -1 ) was stabilized by hydrophobic and van der Waals interactions in combination with hydrogen bonds, as revealed by thermodynamic data (ΔrS° = +17.17 J mol -1 K -1 and ΔrH° = -23.00 kJ mol -1 ), and further supported by molecular docking assessment. Microenvironmental fluctuations around HSA fluorophores and better protein stability against thermal stress were evident due to REG-HSA complexation. Accessibility of both Sudlow's Sites I and II but priority for Site I of the protein for REG was inferred by the competitive ligand displacement and molecular docking assessments. MD simulation results supported the stability of the complex.

show abstract

Use of computational and wet lab techniques to examine the molecular association between a potent hepatitis C virus inhibitor, PSI-6206 and human serum albumin

Abubakar

Mohamed

Halim

et al. 2023

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

View full text Add to dashboard Cite

Biomolecular interaction mechanism of an anticancer drug, pazopanib with human serum albumin: a multi-spectroscopic and computational approach

Cited by 4 publications

References 48 publications

Molecular Recognition Study toward the Mitochondrial Electron Transport Chain Inhibitor Mubritinib and Human Serum Albumin

Molecular Recognition Study toward the Mitochondrial Electron Transport Chain Inhibitor Mubritinib and Human Serum Albumin

Molecular Recognition between Anticancer Drug, Regorafenib and Human Serum Albumin: Interaction Revisited

Use of computational and wet lab techniques to examine the molecular association between a potent hepatitis C virus inhibitor, PSI-6206 and human serum albumin

Contact Info

Product

Resources

About