کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2027643 1542707 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and antitumor evaluation of novel hybrids of phenylsulfonylfuroxan and epiandrosterone/dehydroepiandrosterone derivatives
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Synthesis and antitumor evaluation of novel hybrids of phenylsulfonylfuroxan and epiandrosterone/dehydroepiandrosterone derivatives
چکیده انگلیسی


• Synthesis of hybrids with 16,17-pyrazo-annulated steroids and phenylsulfonylfuroxan.
• The newly synthesized compounds were evaluated as anti-cancer agents.
• Preliminary structure activity relationship was demonstrated.

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 20–1.4 nM against four cell lines (MDA-MB-231, SKOV-3, DU145, and HUVEC), and 1.03 μM 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 1.75 nM and 58 nM, 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 101, September 2015, Pages 7–14
نویسندگان
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