relation: http://publicatio.bibl.u-szeged.hu/29306/
title: Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells
creator:  Girst Gábor
creator:  Lopes Elizabeth A.
creator:  Goncalves Lidia M.
creator:  Espadinha Margarida
creator:  Kúsz Norbert
creator:  Wang Hui-Chun
creator:  Santos Maria M. M.
creator:  Hunyadi Attila
subject: 03.01.06. Farmakológia és gyógyszerészet
description: The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments. The compounds were tested against human breast cancer cell lines MCF-7 (hormone-dependent, wild-type p53) and MDA-MB-231 (triple-negative, mutant p53). Most of the new hybrids were more cytotoxic than their reference fragments and several showed 2-4 times selective toxicity against MDA-MB-231 cells. Relevant pharmacological benefit gained from the hybrid coupling was further confirmed by virtual combination index calculations using the Chou method. Compound 13 modulated doxorubicin-induced DNA damage response through inhibiting the ATR-dependent activation of Chk-1, while increasing the activation of Chk-2. Our results suggest that the new hybrids may serve as new leads against triple negative breast cancer.
date: 2023
type: Folyóiratcikk
type: PeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/29306/1/d3md00251a.pdf
identifier:     Girst Gábor;  Lopes Elizabeth A.;  Goncalves Lidia M.;  Espadinha Margarida;  Kúsz Norbert;  Wang Hui-Chun;  Santos Maria M. M.;  Hunyadi Attila: Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells.   RSC MEDICINAL CHEMISTRY, 14 (9).  pp. 1778-1786.  ISSN 2632-8682 (2023)     
identifier: doi:10.1039/d3md00251a
relation: https://doi.org/10.1039/d3md00251a
relation: 34261677
language: eng
relation: info:eu-repo/semantics/altIdentifier/doi/10.1039/d3md00251a
rights: info:eu-repo/semantics/openAccess