Exploring the interaction of anti-androgen drug-bicalutamide with human alpha-2-macroglobulin: A biophysical investigation.

Bicalutamide (BCT), a drug used in the treatment of prostate cancer, antagonises the actions of androgens, at the receptor level, thereby inhibiting the growth of prostate tumours. Alpha-2-macroglobulin (αM), a pan-proteinase inhibitor, inhibits proteinase, regardless of specificity and catalytic mechanism. αM is deficient in patients of advanced prostate cancer with bone metastases. Our studies explored the interaction of BCT with αM and analysed the BCT induced structural alteration to the αM. The result suggests that BCT decreases the antiproteolytic potential and causes structural and functional change in human αM. UV-visible absorption spectroscopy confirms the formation of αM-BCT complex. Fluorescence analysis shows significant quenching in fluorescence intensity of αM upon binding with BCT. Synchronous fluorescence result suggests the interaction of BCT with αM changed the microenvironment around tyrosine residues. Secondary structure of αM also undergoes a slight change upon complexation with the drug as evident by shift in negative ellipticity in far UV CD spectroscopy. FTIR results confirm the alteration in secondary structure of αM upon drug interaction. Molecular docking studies show that BCT bind to a monomer of αM primarily through hydrophobic force. Thermodynamics parameters were determined by isothermal titration calorimetry found that the binding was exothermic in nature.