Anti-progressive Effects of a Series of Glycinyl and Alaninyl Triazolyl-oxazolidinones on Kelly Neuroblastoma Cell Line
| Autor: | Nada A. Al-Hasawi, Sanaa A. Amine, Leyla H. Sharaf, Ladislav Novotny, Oludotun A. Phillips, Fatma H. Al-Awadhi |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Motility Antineoplastic Agents Neuroblastoma Cell Movement Cell Line Tumor medicine Cell Adhesion Moiety Humans IC50 Oxazolidinones Cell Proliferation Alanine biology Dose-Response Relationship Drug Molecular Structure Chemistry General Medicine Adhesion medicine.disease Fibronectin Oncology Cancer research biology.protein Antibacterial activity |
| Zdroj: | Anticancer research. 40(9) |
| ISSN: | 1791-7530 |
| Popis: | BACKGROUND/AIM Neuroblastoma (NB), the most common extracranial malignant childhood tumor accounts for about 15% of cancer-related deaths in children. Despite the intensive treatment of patients with high-risk scarification of NB, clinical outcomes indicate tumor recurrence greater than 50% and late severe adverse effects. Oxazolidinones are 5-membered heterocyclic compounds with antibacterial activity against resistant bacterial strains. Structural modifications around the oxazolidinone moiety have resulted in derivatives with anti-cancer properties against proliferation, motility, and invasion of breast cancer cells. This study aimed to examine the anti-cancer potential of novel oxazolidinones against a model of a neuroblastoma cell line. MATERIALS AND METHODS Newly synthesized and characterized triazolyl-oxazolidinone derivatives were incubated with neuroblastoma Kelly cells. The anti-proliferation and anti-progression effects of the compounds were evaluated by MTT, and adhesion with migration assays. RESULTS The 5-nitrofuroyl glycinyl-oxazolidinone containing 4-methyltriazolyl group demonstrated the most potent activity with an IC50=6.52 μM. Furthermore, the D-isomer of 5-nitrothiophenecarbonyl alaninyl containing derivative reduced the adhesion to fibronectin by 56.34%, while the D-isomer of 5-nitrofuroyl alaninyl derivative reduced the migration of Kelly cells by 29.14%. CONCLUSION The presence of the 4-methyltriazolyl moiety seems to enhance the anti-proliferative property of triazolyl-oxazolidinone derivatives, as demonstrated by PH-145. There is little or no effect of the stereochemistry of the alanine side-chain on the antiproliferative effect, as demonstrated by the 5-nitrofuroyl D- and L-alaninyl containing derivatives with similar IC50 values. The observed differences in the inhibition of adhesion and migration by the oxazolidinones on Kelly cells provide a new therapeutic approach that needs further investigation. |
| Databáze: | OpenAIRE |
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