Spectroscopic and molecular docking studies on binding interactions of camptothecin drugs with bovine serum albumin

喜树碱类药物与牛血清白蛋白结合相互作用的光谱学和分子对接研究

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Abstract

This study investigates the binding interactions between bovine serum albumin (BSA) and camptothecin (CPT) drugs (camptothecin, 10-hydroxycamptothecin, topotecan, and irinotecan) using UV-Vis spectroscopy, fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, and molecular docking techniques. The fluorescence quenching of BSA by CPT drugs follows a static mechanism, with binding constants (K(b)) ranging from 4.23 × 10(3) M(- 1) (CPT) to 101.30 × 10(3) M(- 1) (irinotecan), demonstrating significant drug binding selectivity. Thermodynamic analysis reveals distinct interaction mechanisms: topotecan binding is driven by hydrogen bonding (ΔH = - 10.96 kJ·mol(- 1)) and hydrophobic interactions (ΔS = 0.066 kJ·mol(- 1)·K(- 1)), while irinotecan exhibits stronger binding dominated by electrostatic forces (ΔH = - 86.77 kJ·mol(- 1)) with significant entropy loss (ΔS = - 0.161 kJ·mol(- 1)·K(- 1)). Molecular docking confirms preferential binding at Sudlow site I of BSA, with hydrophobic interactions and hydrogen bonding as the primary driving forces. These findings provide a comprehensive understanding of CPT-BSA interactions, offering valuable insights for the design of albumin-based drug delivery systems with optimized pharmacokinetic profiles.

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