Recent advancements in cancer research have directed attention towards intercalators, particularly naphthalimide derivatives, which have been extensively studied for their potential as anticancer agents. This investigation aims to assess the cytotoxic effects of six new naphthalimide derivatives containing azo groups, when encapsulated within G0.5 PAMAM dendrimer nanoparticles, utilizing amonafide as a reference drug candidate. Synthesis and characterization of both the derivatives and G0.5 PAMAM dendrimers were conducted using various analytical techniques including mass spectrometry, NMR spectroscopy, and melting point analysis. The formation of nanoparticles was confirmed through TEM, DLS, and zeta potential measurements, revealing uniform nanoscale structures ranging from 10 nm for G0.5 PAMAM dendrimers to 50 nm for the encapsulated drug candidates. Stability of these nanoparticles in neutral pH aqueous solutions was established through DLS and zeta potential data. Encapsulation efficiency (ranging from 13±6 to 54.77±4) and loading capacity (from 49.4±2 to 80.69±3 µM) were determined via HPLC analysis. Assessment of cytotoxicity on MCF7 and A549 cell lines revealed sustained toxicity for the encapsulated drug candidates. Particularly, compound 4d-NP exhibited promising anti-cancer properties with an IC50 value of 23.43±0.18 in MCF7 cells, indicating its potential for further exploration as an anti-cancer agent.

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