Synthesis and Biological Evaluation of Acridine/Acridone Analogs as Potential Anticancer Agents
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
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 (Shariqah (United Arab Emirates)) - 15(2019), 7 vom: 01., Seite 729-737 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Gensicka-Kowalewska, Monika [VerfasserIn] |
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Links: |
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Themen: |
Acridine |
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Anmerkungen: |
Date Completed 06.12.2019 Date Revised 08.01.2020 published: Print Citation Status MEDLINE |
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doi: |
10.2174/1573406414666181015145120 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM289596920 |
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520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a CONCLUSION: Analog 12 could be proposed as the new potential chemotherapeutic against amelanotic melanoma form especially | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Acridine | |
650 | 4 | |a acridone | |
650 | 4 | |a melanoma | |
650 | 4 | |a neuroblastoma | |
650 | 4 | |a retro-tuftsin | |
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650 | 7 | |a Antineoplastic Agents |2 NLM | |
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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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