Design, synthesis, and biological evaluation of hydroquinone derivatives as novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase.

Analogues of the compound 2,5-di-tert-butylhydroquinone (BHQ) are capable of inhibiting the enzyme sarco/endoplasmic reticulum ATPase (SERCA) in the low micromolar and submicromolar concentration ranges. Not only are SERCA inhibitors valuable research tools, but they also have potential medicinal value as agents against prostate cancer. This study describes the synthesis of 13 compounds representing several classes of BHQ analogues, such as hydroquinones with a single aromatic substituent, symmetrically and unsymmetrically disubstituted hydroquinones, and hydroquinones with omega-amino acid tethers attached to their hydroxyl groups.

Structure-based virtual screening for novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase and their experimental evaluation.

A public compound library with 260,000 compounds was screened virtually by computational docking for novel inhibitors of the transmembrane enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). Docking was performed with the program GOLD in conjunction with a high resolution X-ray crystal structure of SERCA. Compounds that were predicted to be active were tested in bioassays.