B and H-NMR Evaluation of Chemical Interactions between Two Polyphenols; Epigallocatechingallate and Quercetin with Bortezomib

Abstract

Bortezomib (Velcade) is a boronic acid dipeptide, proteasome inhibitor drug that its antimyeloma activity in treatment of patients with multiple myeloma (MM) has been approved by FDA. Studies show that consumption of daily diet rich in polyphenols affect Bortezomib’s bioavailability and reduce its antitumor activity. In the present study we made an attempt to investigate the interactions between Bortezomib and some common polyphenols to examine whether these polyphenols interact with the drug. For this purpose, interactions between four dietary polyphenols including: Emodin, Rhein, Epigallocatechingallate (EGCG) and Quercetin with methyl boronic acid, Bortezomib’s substitute, were studied using 1H and 11B- NMR spectroscopy. The results suggest that the vicinal diols in the structure of the two polyphenols (EGCG and Quercetin) interact with the boronic acid moiety of Bortezomib and convert the active triangular boronic acid to an inactive tetrahedral boronate through direct chemical interaction, and this conversion abolishes the antimyeloma activity of Bortezomib. In conclusion, our study suggests that the consumption of dietary sources enriched in EGCG and Quecetin during treatment with Bortezomib in MM patients should be considered.