Design, synthesis and biological evaluation of imidazole and triazole-based carbamates as novel aromatase inhibitors

被引：42

作者：

Ammazzalorso, Alessandra ^{[1
]}

Gallorini, Marialucia ^{[2
]}

Fantacuzzi, Marialuigia ^{[1
]}

Gambacorta, Nicola ^{[3
]}

De Filippis, Barbara ^{[1
]}

Giampietro, Letizia ^{[1
]}

Maccallini, Cristina ^{[1
]}

Nicolotti, Orazio ^{[3
]}

Cataldi, Amelia ^{[2
]}

Amoroso, Rosa ^{[1
]}

机构：

[1] Univ G dAnnunzio, Dept Pharm, Unit Med Chem, Chieti, Italy

[2] Univ G dAnnunzio, Dept Pharm, Unit Anat, Chieti, Italy

[3] A Moro Univ, Dept Farm Sci Farmaco, Unit Med Chem, Bari, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 211卷

关键词：

Aromatase inhibitors; Breast cancer; Cytochrome P450; Carbamates; Imidazole; Triazole;

D O I：

10.1016/j.ejmech.2020.113115

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the search for novel aromatase inhibitors, a series of triazole and imidazole-based carbamate derivatives were designed and synthesized. Final compounds were thus evaluated against human aromatase by in vitro kinetic experiments in a fluorimetric assay in comparison with letrozole. The effect of most active derivatives 13a and 15c was then evaluated in vitro on the human breast cancer cell line MCF7 by MTT assay, cytotoxicity assay (LDH release) and cell cycle analysis, revealing a dose-dependent inhibition profile of cell viability and low micromolar IC50 values. In addition, docking simulations were also carried out to elucidate at a molecular level of detail the binding modes adopted to target human aromatase. (C) 2020 Elsevier Masson SAS. All rights reserved.

引用

页数：11

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