Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents / Monika Gensicka-Kowalewska, Mirosława Cichorek, Anna Ronowska, Milena Deptuła, Ilona Klejbor, Krystyna Dzierzbicka
Background: The lack of efficacious therapy for advanced melanoma and neuroblastoma makes new approaches necessary. Therefore, many scientists seek new, more effective, more selective and less toxic anticancer drugs. Objective: We propose the synthesis of the new functionalized analogs of 1-nitroacridine/4- nitroacridone connected to tuftsin/retro-tuftsin derivatives as potential anticancer agents. Methods: Acridine and acridone analogues were prepared by Ullmann condensation and then cyclization reaction. As a result of nucleophilic substitution reaction 1-nitro-9-phenoxyacridine or 1- chloro-4-nitro-9(10H)-acridone with the corresponding peptides, the planned acridine derivatives (10a-c, 12, 17-a-d, 19) have been obtained. The cytotoxic activity of the newly obtained analogs were evaluated against melanotic (Ma) and amelanotic (Ab) melanoma cell lines and neuroblastoma SH-SY5Y by using the XTT method. Apoptosis and cell cycle were analyzed by flow cytometry. Results: Among the investigated analogs compound 12 exhibited the highest potency comparable to dacarbazine action for amelanotic Ab melanoma cells. FLICA test (flurochrome-labeled inhibitors of caspases) showed that this analog significantly increased the content of cells with activated caspases (C+) among both neuroblastoma lines and only Ab melanoma line. Using phosphatidylserine (PS) externalization assay, 12 induced changes in the Ab melanoma plasma membrane structure as the externalization of phosphatidylserine (An+ cells). These changes in neuroblastoma cells were less pronounced. Conclusion: Analog 12 could be proposed as the new potential chemotherapeutic against amelanotic melanoma form especially.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Medicinal chemistry - 15(2019), 7, Seite 729- |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gensicka-Kowalewska, MonikaMonika [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (9 p) |
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| Förderinstitution / Projekttitel: |
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KFL001033301 |
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| 520 | |a Background: The lack of efficacious therapy for advanced melanoma and neuroblastoma makes new approaches necessary. Therefore, many scientists seek new, more effective, more selective and less toxic anticancer drugs. Objective: We propose the synthesis of the new functionalized analogs of 1-nitroacridine/4- nitroacridone connected to tuftsin/retro-tuftsin derivatives as potential anticancer agents. Methods: Acridine and acridone analogues were prepared by Ullmann condensation and then cyclization reaction. As a result of nucleophilic substitution reaction 1-nitro-9-phenoxyacridine or 1- chloro-4-nitro-9(10H)-acridone with the corresponding peptides, the planned acridine derivatives (10a-c, 12, 17-a-d, 19) have been obtained. The cytotoxic activity of the newly obtained analogs were evaluated against melanotic (Ma) and amelanotic (Ab) melanoma cell lines and neuroblastoma SH-SY5Y by using the XTT method. Apoptosis and cell cycle were analyzed by flow cytometry. Results: Among the investigated analogs compound 12 exhibited the highest potency comparable to dacarbazine action for amelanotic Ab melanoma cells. FLICA test (flurochrome-labeled inhibitors of caspases) showed that this analog significantly increased the content of cells with activated caspases (C+) among both neuroblastoma lines and only Ab melanoma line. Using phosphatidylserine (PS) externalization assay, 12 induced changes in the Ab melanoma plasma membrane structure as the externalization of phosphatidylserine (An+ cells). These changes in neuroblastoma cells were less pronounced. Conclusion: Analog 12 could be proposed as the new potential chemotherapeutic against amelanotic melanoma form especially | ||
| 700 | 1 | |a Cichorek, Mirosława |e verfasserin |4 aut | |
| 700 | 1 | |a Ronowska, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Deptuła, Milena |e verfasserin |4 aut | |
| 700 | 1 | |a Klejbor, Ilona |e verfasserin |4 aut | |
| 700 | 1 | |a Dzierzbicka, Krystyna |e verfasserin |4 aut | |
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