التفاصيل البيبلوغرافية
| العنوان: |
Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells |
| المؤلفون: |
Christos Markatos, Georgia Biniari, Oleg G. Chepurny, Vlasios Karageorgos, Nikos Tsakalakis, Georgios Komontachakis, Zacharenia Vlata, Maria Venihaki, George G. Holz, Theodore Tselios, George Liapakis |
| المصدر: |
Molecules, Vol 29, Iss 17, p 4127 (2024) |
| بيانات النشر: |
MDPI AG, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Organic chemistry |
| مصطلحات موضوعية: |
gonadotropin-releasing hormone, receptor, mitoxantrone, ovarian cancer, cytotoxic drugs, Organic chemistry, QD241-441 |
| الوصف: |
The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7. The subsequent release of mitoxantrone leads to its intracellular accumulation, thus exerting its cytotoxic effects. To test this hypothesis, we determined the cytotoxic effects of Con-3 and Con-7 using the SKOV-3 human OCC. Treatment with Con-3 and Con-7, but not with their unconjugated GnRH counterparts, resulted in the accumulation of mitoxantrone within the SKOV-3 cells, increased their apoptosis, and reduced their proliferation, in a dose- and time-dependent manner, with half-maximal inhibitory concentrations of 0.6–0.9 µM. It is concluded that Con-3 and Con-7 act as cytotoxic “prodrugs” in which mitoxantrone is delivered in a GnRH-R-specific manner and constitute a new class of lead compounds for use as anticancer drugs targeting ovarian tumors. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1420-3049 |
| Relation: |
https://www.mdpi.com/1420-3049/29/17/4127; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules29174127 |
| URL الوصول: |
https://doaj.org/article/629b6733c8b64a05a82d4be18e501779 |
| رقم الانضمام: |
edsdoj.629b6733c8b64a05a82d4be18e501779 |
| قاعدة البيانات: |
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