@misc{10481/101891,
year = {2023},
url = {https://hdl.handle.net/10481/101891},
abstract = {Since the identification of human choline kinase as a protein target against cancer progression, many compounds
have been designed to inhibit its function and reduce the biosynthesis of phosphatidylcholine. Herein, we propose
a series of bioisosteric inhibitors that are based on the introduction of sulphur and feature improved activity
and lipophilic/hydrophilic balance. The evaluation of the inhibitory and of the antiproliferative properties of the
PL (dithioethane) and FP (disulphide) libraries led to the identification of PL 48, PL 55 and PL 69 as the most
active compounds of the series. Docking analysis using FLAP suggests that for hits to leads, binding mostly involves
an interaction with the Mg2+ cofactor, or its destabilization. The most active compounds of the two series
are capable of inducing apoptosis following the mitochondrial pathway and to significantly reduce the expression
of anti-apoptotic proteins such as the Mcl-1. The fluorescence properties of the compounds of the PL library
allowed the tracking of their mode of action, while PAINS (Pan Assays Interference Structures) filtration databases
suggest the lack of any unspecific biological response.},
organization = {Ministerio de Innovación y Ciencia [PID2019-109294RB-I00]},
organization = {FEDER 2020 [B-CTS-216- UGR20]},
organization = {ERDF  [No. 1.1.1.5/19/A/004]},
organization = {Latvian Council of Science [lzp-2020/2-0013]},
publisher = {Elsevier},
keywords = {Antitumoral drug},
keywords = {Choline kinase inhibition},
keywords = {Bioisosterism},
keywords = {Environmental synthesis},
title = {New bioisosteric sulphur-containing choline kinase inhibitors with a tracked mode of action},
doi = {10.1016/j.ejmech.2022.115003},
author = {Luque Navarro, Pilar María and Carrasco Jiménez, María Paz and Goracci, Laura and Paredes Martínez, José Manuel and Espinar Barranco, Laura and Valverde Pozo, Javier and Torretta, Archimede and Parisini, Emilio and Mariotto, Elena and Marchioro, Chiara and Laso, Alejandro and Marco De La Calle, Carmen and Viola, Giampietro and Lanari, Daniela and López Cara, Luisa Carlota},
}