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Journal of Chemistry
Volume 2017 (2017), Article ID 2370359, 9 pages
Research Article

Synthesis and Experimental Validation of New PDI Inhibitors with Antiproliferative Activity

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, Italy

Correspondence should be addressed to Francesca Aiello

Received 2 April 2017; Revised 3 May 2017; Accepted 9 May 2017; Published 15 June 2017

Academic Editor: Joaquin Campos

Copyright © 2017 Mariateresa Badolato et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily of redox enzymes. PDI is a multifunctional protein that catalyzes disulfide bond formation, cleavage, and rearrangement in unfolded or misfolded proteins and functions as a chaperone in the endoplasmic reticulum. Besides acting as a protein folding catalyst, several evidences have suggested that PDI can bind small molecules containing, for example, a phenolic structure, which includes the estrogenic one. Increasing studies indicate that PDI is involved in both physiology and pathophysiology of cells and tissues and is involved in the survival and proliferation of different cancers. Propionic acid carbamoyl methyl amides (PACMAs) showed anticancer activity in human ovarian cancer, both in vitro and in vivo, by inhibiting PDI. The inhibition of PDI’s activity may have a therapeutic role, in various diseases, including cancer. In the present study, we designed and synthesized a diversified small library of compounds with the aim of identifying a new class of PDI inhibitors. Most of synthesized compounds showed a good inhibitory potency against PDI and particularly 4-methyl substituted 2,6-di-tert-butylphenol derivatives (8–10) presented an antiproliferative activity in a wide panel of human cancer cell lines, including ovarian ones.