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Synthesis and antitumor evaluation of novel hybrids of phenylsulfonylfuroxan and epiandrosterone/dehydroepiandrosterone derivatives.
- Source :
-
Steroids [Steroids] 2015 Sep; Vol. 101, pp. 7-14. Date of Electronic Publication: 2015 May 22. - Publication Year :
- 2015
-
Abstract
- Thirteen novel furoxan-based nitric oxide (NO) releasing hybrids (14a-e, 15a-e, 17b-d) of 16,17-pyrazo-annulated steroidal derivatives were synthesized and evaluated against the MDA-MB-231, HCC1806, SKOV-3, DU145, and HUVEC cell lines for their in vitro anti-proliferative activity. Most of the compounds displayed potent anti-proliferative effects. Among them, 17c exhibited the best activity with IC50 values of 20-1.4nM against four cell lines (MDA-MB-231, SKOV-3, DU145, and HUVEC), and 1.03μM against a tamoxifen resistant breast cancer cell line (HCC1806). Furthermore, five compounds (14a, 15a, 17b-d) were selected to screen for VEGF inhibitory activity. Compounds 15a, 17b,c showed obviously better activity than 2-Methoxyestradiol (2-ME) on reducing levels of VEGF secreted by MDA-MB-231 cell line. In a Capillary-like Tube Formation Assay, compounds 17b,c exhibited a significant suppression of the tubule formation in the concentration of 1.75nM and 58nM, respectively. The preliminary SAR showed that steroidal scaffolds with a linker in 3-position were favorable moieties to evidently increase the bioactivities of these hybrids. Overall, these results implied that 17c merited to be further investigated as a promising anti-cancer candidate.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Chemistry Techniques, Synthetic
Humans
Oxadiazoles chemistry
Vascular Endothelial Growth Factor A antagonists & inhibitors
Androsterone analogs & derivatives
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Dehydroepiandrosterone analogs & derivatives
Oxadiazoles chemical synthesis
Oxadiazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5867
- Volume :
- 101
- Database :
- MEDLINE
- Journal :
- Steroids
- Publication Type :
- Academic Journal
- Accession number :
- 26004429
- Full Text :
- https://doi.org/10.1016/j.steroids.2015.05.003