Substitutional Diversity-Oriented Synthesis and In Vitro Anticancer Activity of Framework-Integrated Estradiol-Benzisoxazole Chimeras
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 aroma...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2022
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| Sorozat: | MOLECULES
27 No. 21 |
| Tárgyszavak: | |
| doi: | 10.3390/molecules27217456 |
| mtmt: | 33206020 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/25697 |
| LEADER | 02515nab a2200289 i 4500 | ||
|---|---|---|---|
| 001 | publ25697 | ||
| 005 | 20221206094957.0 | ||
| 008 | 221206s2022 hu o 0|| Angol d | ||
| 022 | |a 1420-3049 | ||
| 024 | 7 | |a 10.3390/molecules27217456 |2 doi | |
| 024 | 7 | |a 33206020 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a Angol | ||
| 100 | 1 | |a Kovács Ferenc | |
| 245 | 1 | 0 | |a Substitutional Diversity-Oriented Synthesis and In Vitro Anticancer Activity of Framework-Integrated Estradiol-Benzisoxazole Chimeras |h [elektronikus dokumentum] / |c Kovács Ferenc |
| 260 | |c 2022 | ||
| 300 | |a 26 | ||
| 490 | 0 | |a MOLECULES |v 27 No. 21 | |
| 520 | 3 | |a 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. | |
| 650 | 4 | |a Kémiai tudományok | |
| 650 | 4 | |a Biológiai tudományok | |
| 700 | 0 | 1 | |a Adamecz Dóra Izabella |e aut |
| 700 | 0 | 1 | |a Nagy Ferenc István |e aut |
| 700 | 0 | 1 | |a Papp Benedek |e aut |
| 700 | 0 | 2 | |a Csontné Kiricsi Mónika |e aut |
| 700 | 0 | 2 | |a Nagyné Frank Éva |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/25697/1/molecules-27-07456.pdf |z Dokumentum-elérés |