Design and biological evaluation of a quinoline-substituted silicon phthalocyanines for photodynamic therapy of endometrial cancer: topoisomerase IIα targeting and apoptosis induction

Abstract

In this study, to discover potentially selective and safe therapeutic candidates for photodynamic therapy (PDT), new quinoline-derived silicon phthalocyanine compounds (8K-C3-D-Si and 8K-C3-D-SiQ) were synthesized, characterized, and their PDT potential was evaluated. The synthesized compounds were characterized using spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, MS, and UV–Vis. In photochemical measurements, the singlet oxygen production capacities and photostabilities of the compounds were investigated, and observed that 8K-C3-D-SiQ exhibited a higher effectiveness (ΦΔ = 0.088 ± 0.009 for 8K-C3-D-Si and ΦΔ = 0.345 ± 0.034 for 8K-C3-D-SiQ). The IC50 value of 8K-C3-D-SiQ in the human endometrial cancer cell line (HEC-1B) after 24 h of incubation in the presence of light was found to be 84.18 ± 14.84 nM. In cells treated with 0.1 μM 8K-C3-D-SiQ, late apoptosis was detected at 54.03 ± 3.10% and necrosis at 22.74 ± 5.98% under light exposure. At the molecular level, western blot results showed increased p53 and cytochrome c expression and suppression of topoisomerase IIα (Topo-IIα). Ab initio quantum mechanics (QM) predicted its electronic structure and molecular docking with DNA-Topo-II complex indicated that, with a unique binding, 8K-C3-D-SiQ could wrap around the DNA G-segment with two 1-methylquinolinium-8-oxypropyl substituents occupying both DNA cleavage sites. In conclusion, 8K-C3-D-SiQ may be considered a promising candidate for PDT due to its high singlet oxygen production, potent phototoxicity, topoisomerase inhibition, and apoptosis induction.