Novel Monoazo Dispersion Dyes Incorporating a 4-thiazolidinone Moiety: Synthesis, Structural Characterization,...

In our method for synthesizing potent anticancer derivatives against both liver and breast tumors, a series of novel azo dispersion dyes was produced by coupling salicylaldehyde with diazonium ions derived from aryl amines to evaluate their anticancer efficacy while ensuring high safety for human normal cells.

The diazenyl thiosemicarbazones (3a-f), resulting from the reaction of 5-arylazo-2-hydroxybenzaldehyde (1a-f) with thiosemicarbazide, subsequently reacted with ethyl chloroacetate to yield a series of diazenyl-4-thiazolidinones (4a-f). The chemical structures of these derivatives were well-characterized utilizing numerous analytical approaches, including FT-IR, 13C-NMR, 1H-NMR, and UV-Visible spectroscopy. Furthermore, the synthesized derivatives were assessed for their anticancer activity against HepG2 (liver cancer) and MDA-MB-231 (breast cancer) cell lines, compared to normal HSF cells.

The synthesized compounds exhibited anticancer activity while maintaining high safety for normal cells. Compounds 3f, 4d, and 4f demonstrated significant cytotoxic efficacy against HepG2 cells, with selectivity index (SI) values of 109.47, 116.63, and 116.48, respectively. Additionally, the SI of the same compounds 3f (78.18), 4d (48.91), and 4f (71.82) displayed the highest cytotoxic property against MDA-MB-231 cells. Remarkably, neither of the tested azo compounds (3f and 4f) caused any detectable damage to normal skin cells. The findings of the molecular docking investigation were consistent with the biological assessments.

The new synthesized diazenyl thiosemicarbazones have demonstrated potent anticancer activity. This is due to the presence of electron-donating groups at the para position of the diazo ring. The positive charge generated in this cationic form facilitates their adhesion to the negatively charged surfaces of the cell membrane of the treated cancer cells and enhances their permeability. However, some limitations of this study warrant further examination, such as the lack of a comprehensive pharmacokinetic analysis and long-term safety assessments. Furthermore, the pharmacokinetics and immunogenicity of the newly synthesized derivatives have not been studied. Furthermore, further research is needed to explore the effects of the synthetic derivatives in various animal models. These features should be investigated in future studies to clearly clarify the therapeutic potential and systemic performance of the synthesized derivatives.

This study suggests that compounds 3f and 4f are very selective anticancer agents. in silico ADMET investigation exposed the superior pharmacokinetic properties of the newly synthesized derivatives and can serve to offer valuable insight for developing an effective cancer therapy.