Academic Journal
Organometallic Titanocene–Gold Compounds as Potential Chemotherapeutics in Renal Cancer. Study of their Protein Kinase Inhibitory Properties
| العنوان: | Organometallic Titanocene–Gold Compounds as Potential Chemotherapeutics in Renal Cancer. Study of their Protein Kinase Inhibitory Properties |
|---|---|
| المؤلفون: | Fernández-Gallardo, Jacob, Elie, Benelita T., Sulzmaier, Florian J., Sanaú, Mercedes, Ramos, Joe W., Contel, María |
| المصدر: | Publications and Research |
| بيانات النشر: | CUNY Academic Works |
| سنة النشر: | 2015 |
| المجموعة: | City University of New York: CUNY Academic Works |
| الوصف: | Early–late transition metal TiAu2 compounds [(η-C5H5)2Ti{OC(O)CH2PPh2AuCl}2] (3) and new [(η-C5H5)2Ti{OC(O)-4-C6H4PPh2AuCl}2] (5) were evaluated as potential anticancer agents in vitro against renal and prostate cancer cell lines. The compounds were significantly more effective than monometallic titanocene dichloride and gold(I) [{HOC(O)RPPh2}AuCl] (R = −CH2– 6, −4-C6H4– 7) derivatives in renal cancer cell lines, indicating a synergistic effect of the resulting heterometallic species. The activity on renal cancer cell lines (for 5 in the nanomolar range) was considerably higher than that of cisplatin and highly active titanocene Y. Initial mechanistic studies in Caki-1 cells in vitro coupled with studies of their inhibitory properties on a panel of 35 kinases of oncological interest indicate that these compounds inhibit protein kinases of the AKT and MAPKAPK families with a higher selectivity toward MAPKAPK3 (IC503 = 91 nM, IC505 = 117 nM). The selectivity of the compounds in vitro against renal cancer cell lines when compared to a nontumorigenic human embryonic kidney cell line (HEK-293T) and the favorable preliminary toxicity profile on C57black6 mice indicate that these compounds (especially 5) are excellent candidates for further development as potential renal cancer chemotherapeutics. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://academicworks.cuny.edu/gc_pubs/235; https://academicworks.cuny.edu/context/gc_pubs/article/1254/viewcontent/PMC4245150.pdf |
| الاتاحة: | https://academicworks.cuny.edu/gc_pubs/235 https://academicworks.cuny.edu/context/gc_pubs/article/1254/viewcontent/PMC4245150.pdf |
| رقم الانضمام: | edsbas.2CF47E45 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |