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 - Publikacja - MOST Wiedzy

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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

Abstrakt

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) inhibitors for the treatment of breast cancer. Prompted by promising biological results and in silico analysis, the initial series of similar compounds were extended, appending a variety of m-substituents at the outer phenyl ring. The inhibition profiles of the newly synthesized compounds were evaluated using a radioisotope enzymatic assay and, together with the preceding reported derivatives, using a radioisotope assay in MCF-7 cells. The most active compound, 5l, demonstrated an extraordinary STS inhibitory potency in MCF-7 cells with an IC50 value improved 5-fold compared to that of the reference Irosustat (0.21 vs 1.06 nM). The five most potent compounds were assessed in vivo in a 67NR mouse mammary gland cancer model, with 4b measured to induce up to 51% tumor growth inhibition at 50 mg/kg with no evidence of side effects and toxicity.

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Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuły w czasopismach
Opublikowano w:
JOURNAL OF MEDICINAL CHEMISTRY nr 65, strony 5044 - 5056,
ISSN: 0022-2623
Język:
angielski
Rok wydania:
2022
Opis bibliograficzny:
Biernacki K., Ciupak O., Daśko M., Rachon J., Kozak W., Rak J., Kubiński K., Masłyk M., Martyna A., Śliwka-Kaszyńska M., Wietrzyk J., Świtalska M., Nocentini A., Supuran C. T., Demkowicz S.: 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// JOURNAL OF MEDICINAL CHEMISTRY -Vol. 65,iss. 2 (2022), s.5044-5056
DOI:
Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1021/acs.jmedchem.1c02220
Źródła finansowania:
Weryfikacja:
Politechnika Gdańska

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