Biomaterial Database

Design, synthesis and biological evaluation of imidazole and triazole-based carbamates as novel aromatase inhibitors. 2021

Alessandra Ammazzalorso, and Marialucia Gallorini, and Marialuigia Fantacuzzi, and Nicola Gambacorta, and Barbara De Filippis, and Letizia Giampietro, and Cristina Maccallini, and Orazio Nicolotti, and Amelia Cataldi, and Rosa Amoroso

Unit of Medicinal Chemistry, Department of Pharmacy, "G. D'Annunzio" University, Chieti, Italy. Electronic address: alessandra.ammazzalorso@unich.it.

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.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D002219	Carbamates	Derivatives of carbamic acid, H2NC(	Carbamate,Aminoformic Acids,Carbamic Acids,Acids, Aminoformic,Acids, Carbamic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014230	Triazoles	Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.	Triazole
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D047072	Aromatase Inhibitors	Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.	Aromatase Inhibitor,Inhibitor, Aromatase,Inhibitors, Aromatase