Heterocyclic androstane derivatives targeting hormone-related cancers: Synthesis, bioactivity and docking studies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F25%3A00638430" target="_blank" >RIV/61389030:_____/25:00638430 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/25:73631054

Result on the web

<a href="https://doi.org/10.1016/j.ejmech.2025.117850" target="_blank" >https://doi.org/10.1016/j.ejmech.2025.117850</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2025.117850" target="_blank" >10.1016/j.ejmech.2025.117850</a>

Result language

angličtina

Original language name

Heterocyclic androstane derivatives targeting hormone-related cancers: Synthesis, bioactivity and docking studies

Original language description

Insertion of a heterocyclic ring into the steroid core could enhance bioactivity, improve selectivity and reduce side effects in potential drugs for cancer therapy. The present study describes the synthesis of new thiazoline, thiadiazoline and thiazolidinone steroid compounds combined with lactone, lactam or pyridine moieties. These steroid hybrid molecules may be potential candidates for drug design, with improved biological activity and bioavailability. The starting androstenedione or dehydroepiandrosterone were modified by multiphase synthesis into thiosemicarbazone androstane derivatives, direct precursors for the synthesis of new heterocyclic compounds. Their cytotoxicity was tested against five cancer cell lines: breast adenocarcinoma cells (MCF7), acute lymphoblastic leukemia (CCRF-CEM), cervical carcinoma cells (HeLa), hormone-independent (DU 145) and hormone-sensitive prostate cancer cells (LNCaP), as well as against normal skin fibroblasts (BJ). Compounds 5 and 16 were found to be the most selective, with both inducing apoptosis in HeLa cells. New compounds were also evaluated for their relative binding affinities for the ligand-binding domains (LBDs) of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR) or glucocorticoid receptor (GR) using a fluorescent assay in yeast cells, where thiazole derivative 13 exhibited the highest binding affinity for ER alpha, while thiazolidinone 7 showed strong selective affinity for ER beta. Furthermore, inhibition potential against human aldo-keto reductase 1C3 and 1C4 (AKR1C3 and AKR1C4) was evaluated by fluorescence spectroscopy, with acetamido thiadiazoline 21 displaying an IC50 value for AKR1C3 slightly higher than the reference inhibitor ibuprofen. Molecular docking studies were used to propose protein-ligand binding models for compounds showing the strongest affinity toward specific proteins based on in vitro experiments. In summary, our results suggest that the tested heterocyclic derivatives are active against hormone-dependent cancer cells and represent promising leads for the development of novel therapeutics.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

Project

<a href="/en/project/GA23-05474S" target="_blank" >GA23-05474S: Modulation of kinases for targeted treatment of haematological and other malignancies</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

1768-3254

Volume of the periodical

296

Issue of the periodical within the volume

OCT 15

Country of publishing house

FR - FRANCE

Number of pages

18

Pages from-to

117850

UT code for WoS article

001517297600001

EID of the result in the Scopus database

2-s2.0-105007629030