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