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.
Method: 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
was evaluated against melanotic (Ma) and amelanotic (Ab) melanomacell 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.
Keywords: acridine, acridone, tuftsin, retro-tuftsin, melanoma, neuroblastoma
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