Development of Sulfamoylated 4-(1-Phenyl-1H-1,2,3-triazol-4-yl)phenol Derivatives as Potent Steroid Sulfatase Inhibitors for Efficient Treatment of Breast Cancer

We present here the advances achieved in the development of new sulfamoylated 4-(1-phenyl-1H-1,2,3-triazol-4-yl)phenol derivatives as potent steroid sulfatase (STS) inhibitorsfor the treatment of breast cancer. Prompted by promisingbiological results and in silico analysis, the initial series of similarcompounds were extended, appending a variety of m-substituentsat the outer phenyl ring. The inhibition profiles of the newlysynthesized compounds were evaluated using a radioisotopeenzymatic assay and, together with the preceding reportedderivatives, using a radioisotope assay in MCF-7 cells. The mostactive compound,5l, demonstrated an extraordinary STSinhibitory potency in MCF-7 cells with an IC50value improved5-fold compared to that of the referenceIrosustat(0.21 vs 1.06nM). Thefive most potent compounds were assessed in vivo in a 67NR mouse mammary gland cancer model, with4bmeasured to induce up to 51% tumor growth inhibition at 50 mg/kg with no evidence of side effects and toxicity

Automated summary

This research presents the development of new sulfamoylated 4-(1-phenyl-1H-1,2,3-triazol-4-yl)phenol derivatives as potential steroid sulfatase (STS) inhibitors for breast cancer treatment. The compounds showed promising inhibitory activity in in vitro and in vivo assays, with compound 5l demonstrating the most potent inhibition in MCF-7 cells and compound 4b showing significant tumor growth inhibition without side effects or toxicity in a mouse model.