Non-peripheral octasubstituted zinc(II) phthalocyanines bearing pyridinepropoxy substituents – Antibacterial, anticancer photodynamic and sonodynamic activity

• Published in: Journal of inorganic biochemistry 2025-01, Vol.262, p.112751, Article 112751
• Main Authors: Wysocki, Marcin, Ziental, Daniel, Biyiklioglu, Zekeriya, Jozkowiak, Malgorzata, Baş, Hüseyin, Dlugaszewska, Jolanta, Piotrowska-Kempisty, Hanna, Güzel, Emre, Sobotta, Lukasz
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bacteria; Cell Line, Tumor; Humans; Indoles - chemistry; Indoles - pharmacology; Isoindoles; Methicillin-Resistant Staphylococcus aureus - drug effects; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Phthalocyanine; Pyridines - chemistry; Pyridines - pharmacology; Sensitizer; Singlet Oxygen - metabolism; Sonodynamic therapy; Staphylococcus epidermidis - drug effects; Zinc Compounds
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112751

The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran – DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and S. epidermidis. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications. [Display omitted] •Studied phthalocyanines are stabile under light and ultrasounds exposition.•Pyridinepropoxy-substituted phthalocyanines reveal high singlet oxygen production.•Novel phthalocyanines are active against bacteria upon irradiation and sonication.