RT journal article
T1 Analogues of Natural Chalcones as Efficient Inhibitors of AKR1C3
A1 Möller, Gabriele
A1 Temml, Veronika
A1 Cala Peralta, Antonio
A1 Gruet, Océane
A1 Richomme, Pascal
A1 Seraphin, Denis
A1 Viault, Guillaume
A1 Kraus, Luisa
A1 Huber-Cantonati, Petra
A1 Schopfhauser, Elisabeth
A1 Pachmayr, Johanna
A1 Tokarz, Janina
A1 Schuster, Daniela
A1 Helesbeux, Jean-Jacques
A1 Allen Dyar, Kenneth
A2 Química Orgánica
K1 chalcone
K1 aldo-keto reductase
K1 cancer
K1 AKR1C3
K1 17β-hydroxysteroid dehydrogenase
K1 3α-hydroxysteroid dehydrogenase
K1 structure-activity relationship
AB Naturally occurring substances are valuable resources for drug development. In this respect, chalcones are known to be antiproliferative agents against prostate cancer cell lines through various mechanisms or targets. Based on the literature and preliminary results, we aimed to study and optimise the efficiency of a series of chalcones to inhibit androgen-converting AKR1C3, known to promote prostate cancer. A total of 12 chalcones with different substitution patterns were synthesised. Structure–activity relationships associated with these modifications on AKR1C3 inhibition were analysed by performing enzymatic assays and docking simulations. In addition, the selectivity and cytotoxicity of the compounds were assessed. In enzymatic assays, C-6′ hydroxylated derivatives were more active than C-6′ methoxylated derivatives. In contrast, C-4 methylation increased activity over C-4 hydroxylation. Docking results supported these findings with the most active compounds fitting nicely in the binding site and exhibiting strong interactions with key amino acid residues. The most effective inhibitors were not cytotoxic for HEK293T cells and selective for 17β-hydroxysteroid dehydrogenases not primarily involved in steroid hormone metabolism. Nevertheless, they inhibited several enzymes of the steroid metabolism pathways. Favourable substitutions that enhanced AKR1C3 inhibition of chalcones were identified. This study paves the way to further develop compounds from this series or related flavonoids with improved inhibitory activity against AKR1C3.
PB MDPI
SN 2218-1989
YR 2022
FD 2022-01-21
LK http://hdl.handle.net/10498/35222
UL http://hdl.handle.net/10498/35222
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026