%0 Journal Article
%@ 1420-3049
%A  Kovács Ferenc
%A  Adamecz Dóra Izabella
%A  Nagy Ferenc István
%A  Papp Benedek
%A  Csontné Kiricsi Mónika
%A  Nagyné Frank Éva
%A Kémia Doktori Iskola SZTE / DI KDI [2000-],
%A Szerves Kémiai Tanszék SZTE / TTIK / KI SZT [2016-],
%A Biokémiai és Molekuláris Biológiai Tanszék SZTE / TTIK / BI BMBT [2016-],
%D 2022
%F publicatio:25697
%J MOLECULES
%N 21
%T Substitutional Diversity-Oriented Synthesis and In Vitro Anticancer Activity of Framework-Integrated Estradiol-Benzisoxazole Chimeras
%U http://publicatio.bibl.u-szeged.hu/25697/
%V 27
%X Hybridization of steroids and other pharmacophores often modifies the bioactivity of the parent compounds, improving selectivity and side effect profile. In this study, estradiol and 3′-(un)substituted benzisoxazole moieties were combined into novel molecules by structural integration of their aromatic rings. Simple estrogen starting materials, such as estrone, estradiol and estradiol-3-methylether were used for the multistep transformations. Some of the heterocyclic derivatives were prepared from the estrane precursor by a formylation or Friedel–Crafts acylation—oximation—cyclization sequence, whereas others were obtained by a functional group interconversion strategy. The antiproliferative activities of the synthesized compounds were assessed on various human cervical, breast and prostate cancer cell lines (HeLa, MCF-7, PC3, DU-145) and non-cancerous MRC-5 fibroblast cells. Based on the primary cytotoxicity screens, the most effective cancer-selective compounds were selected, their IC50 values were determined and their apoptosis-inducing potential was evaluated by quantitative real-time PCR. Pharmacological studies revealed a strong structure–function relationship, where derivatives with a hydroxyl group on C-17 exhibited stronger anticancer activity compared to the 17-acetylated counterparts. The present study concludes that novel estradiol-benzisoxazole hybrids exert remarkable cancer cell-specific antiproliferative activity and trigger apoptosis in cancer cells.