Bortezomib (VELCADETM) is an effective chemotherapeutic approved for the treatment multiple myeloma. Chemotherapeutic strategies often include supplemental anticancer agents to scavenge reactive oxygen species. Bortezomib, a dipeptidylboronic acid, may be reactive with these antioxidants considering the reactivity of boronic acids with 1,2- and 1,3-diols, thereby reducing it’s efficacy. In this study the heats of formation at 298.15 K of o-N,N-dimethylamine phenylboronic acid (a boronic acid analogue of bortezomib), with routinely used chemotherapeutic supplements vitamin C, dexamethasone, and epigallocatechin gallate (EGCG) (the active compound in green tea extract) have been calculated using the Density Functionals B3LYP, PBE1PBE, ω-B97x-D with the Pople-type basis sets 6-31+G(d) and 6-311++G(d,p). The heats of formation are used to determine the enthalpy changes for the dehydration reactions: R–B(OH)2 + antioxidant --&gt; R–B(O-R1,O-R2) + 2 H2O and R–B(OH)2 + antioxidant --&gt; R–B(OH)(O-R1) + H2O. Enthalpy changes for the dehydration reactions reactions are consistently predicted to be exothermic for the antioxidants vitamin C, and EGCG. Boronic acid reactions with dexamethasone are consistently endothermic. Our results indicate anticancer supplements with flexible or accessible diol moieties may be detrimental to bortezomib treatment strategies.

Computational study of the dehydration of bortezomib from common antioxidants

251st National Meeting (2016)

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