Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/13898
Title: Human estrogen receptor α antagonists, part 2: Synthesis driven by rational design, in vitro antiproliferative, and in vivo anticancer evaluation of innovative coumarin-related antiestrogens as breast cancer suppressants
Authors: Kurtanović, Nezrina
Tomašević, Nevena
Matić, Sanja
Mitrovic, Marina
Kostić D.
Sabatino M.
Antonini L.
Ragno, Rino
Mladenović, Milan
Issue Date: 2022
Abstract: New twelve in silico designed coumarin-based ERα antagonists, namely 3DQ-1a to 3DQ-1е, were synthesized and confirmed as selective ERα antagonists, showing potencies ranging from single-digit nanomolar to picomolar. The hits were confirmed as selective estrogen receptor modulators and validated as antiproliferative agents using MCF-7 breast cancer cell lines exerting from picomolar to low nanomolar potency, at the same time showing no agonistic activity within endometrial cell lines. Their mechanism of action was inspected and revealed to be through the inhibition of the Raf-1/MAPK/ERK signal transduction pathway, preventing hormone-mediated gene expression on either genomic direct or genomic indirect level, and stopping the MCF-7 cells proliferation at G0/G1 phase. In vivo experiments, by means of the per os administration to female Wistar rats with pre-induced breast cancer, distinguished six derivatives, 3DQ-4a, 3DQ-2a, 3DQ-1a, 3DQ-1b, 3DQ-2b, and 3DQ-3b, showing remarkable potency as tumor suppressors endowed with optimal pharmacokinetic profiles and no significant histopathological profiles. The presented data indicate the new compounds as potential candidates to be submitted in clinical trials for breast cancer therapy.
URI: https://scidar.kg.ac.rs/handle/123456789/13898
Type: article
DOI: 10.1016/j.ejmech.2021.113869
ISSN: 0223-5234
SCOPUS: 2-s2.0-85117851089
Appears in Collections:Faculty of Medical Sciences, Kragujevac
Faculty of Science, Kragujevac
Institute for Information Technologies, Kragujevac

Page views(s)

189

Downloads(s)

6

Files in This Item:
File Description SizeFormat 
PaperMissing.pdf
  Restricted Access
29.86 kBAdobe PDFThumbnail
View/Open


Items in SCIDAR are protected by copyright, with all rights reserved, unless otherwise indicated.