Platinum drugs binding to human serum albumin: Effect of non-steroidal anti-inflammatory drugs

• Interactions between human serum albumin and platinum complexes have effect on the structure of protein.
• The binding process caused microenvironmental and conformational changes in albumin.
• The binding site for platinum complexes in HSA is located in subdomains IIA and IIIA.
• The cisplatin has a higher affinity to subdomain IIA than IIIA.
• Structural changes in albumin inducted by the NSAIDs lead to partial blockage of cisplatin coordination in subdomains IIA and IIIA.

In this report, we provide investigations about the effect of Sudlow's site I and II blockers on the platinum anticancer drugs binding. The effect of warfarin, aspirin, ibuprofen and meloxicam on the platinum binding to HSA has been investigated through gel-filtration chromatography, UV–vis, CD, fluorescence spectroscopy and the inductively coupled plasma atomic emission spectroscopy (ICP(AES)) method.The results confirm that the platinum complexes bind to Sudlow's site I and II. Modifications of the protein structure caused by non-steroidal anti-inflammatory drugs (NSAIDs) that bind in these areas have an impact on the amount of cisplatin bound to albumin. The number of bound cisplatin was reduced by approximately 30–40% compared to the native protein.

Structural changes in albumin inducted by pharmacologically important new generation, non-steroidal anti-inflammatory drug meloxicam and popular traditional non-steroidal anti-inflammatory drugs: aspirin and ibuprofen lead to partial blockage of cisplatin coordination in subdomains IIA and IIIA. As a result, NSAIDs cause an increased the amount of free fraction of the drug.Figure optionsDownload as PowerPoint slide