Unusual human serum albumin fibrillation inhibition by ketoprofen and fenoprofen: Mechanistic insights

Development of efficient therapeutic strategies to combat protein misfolding and fibrillation is of great clinical significance. In the current study, efforts have been made to obtain qualitative and quantitative insights into interactions of anti-inflammatory drugs; ketoprofen and fenoprofen with the transport protein HSA and their inhibitory action on fibrillation by employing a combination of calorimetric, spectroscopic, microscopic, and molecular docking methods. Interestingly, both ketoprofen and fenoprofen are able to completely inhibit fibrillation of HSA when added at a concentration of 0.5 mM for fenoprofen or 1 mM ketoprofen. Further, no amorphous aggregates are formed. Isothermal titration calorimetric studies highlight the predominant role of polar interactions of these drugs with protein in prevention of fibrillation. The role of conformational flexibility of benzoyl and phenoxy groups of drugs has been correlated with inhibition efficiency. Such studies highlight the role of functionality required for an inhibitor in addressing neurodegenerative diseases.

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