Multifunctional 1,3,4-Oxadiazole derivative-substituted phthalocyanines: Exploring Sono/photodynamic, antimicrobial, anticancer, and enzyme inhibitory activities with in silico analysis
Journal of Photochemistry and Photobiology A: Chemistry, cilt.485, 2027 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 485
- Basım Tarihi: 2027
- Doi Numarası: 10.1016/j.jphotochem.2026.117792
- Dergi Adı: Journal of Photochemistry and Photobiology A: Chemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: Anti-bacterial, Anti-cancer, Anti-oxidant, In silico, Phthalocyanine, Singlet oxygen, Sono-photochemical
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
In this study, a novel ligand (1) compound incorporating a 1,3,4-oxadiazole derivative moiety was synthesized and reported for the first time. Utilizing this newly developed ligand (1) , a series of non-peripherally tetra-substituted phthalocyanine derivatives (2–4) containing zinc (II), gallium (III) chloride, and indium (III) chloride as central metal ions were successfully synthesized. These metallophthalocyanines (2–4) , featuring 1,3,4-oxadiazole derivative groups at non-peripheral positions, were designed to explore enhanced biological and physicochemical properties. Comprehensive structural and spectroscopic characterizations of the synthesized compounds were conducted using Ultraviolet-visible spectroscopy (UV–Vis), Fourier-transform infrared (FT-IR) spectroscopy, Nuclear magnetic resonance (NMR) spectroscopy, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and Scanning electron microscopy (SEM). The findings contribute valuable insights into the development of functionally enhanced phthalocyanines for potential applications in biomedical and material sciences. The effectiveness of photochemical and sono-photochemical strategies in promoting singlet oxygen (1O2) generation crucial for successful photodynamic therapy was systematically investigated. The newly developed phthalocyanine derivatives exhibited notable quantum yields of singlet oxygen. Specifically, under conventional photochemical activation, complexes (2–4) achieved ΦΔ values of 0.55, 0.71, and 0.51, respectively. When subjected to combined ultrasound and light irradiation, these values increased to 0.77, 0.95, and 0.82, highlighting the enhanced performance of the compounds under dual activation conditions. The cytotoxic effects of the compounds on A549 lung cancer and C6 glioma cell lines were evaluated using the MTT test. Additionally, the inhibitory effects of the compounds on CA I and CA II enzymes were investigated. The results showed that these compounds inhibited CA I and CA II enzymes in a dose-dependent manner, and also had an effect that enhanced the destruction of cancer cells. Antimicrobial susceptibility testing was conducted using the broth microdilution method in accordance with CLSI and EUCAST guidelines. Minimum inhibitory concentration (MIC) values were determined for Pseudomonas aeruginosa, Bacillus cereus, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli , and Candida albicans ATCC reference strains. The tested compounds exhibited antibacterial activity primarily against B. cereus , S. aureus , and E. coli , while no antifungal activity was observed against C. albicans . These findings suggest that metal phthalocyanine derivatives possess intrinsic antibacterial properties and may serve as a foundation for further antimicrobial research. The ABTS radical cation scavenging IC50 values were 7149 ± 0.98, 6126 ± 0.63, and 2164 ± 1.35 μg/mL for Zn(II)Pc (2) , Ga(III)ClPc (3) , and In(III)ClPc (4) , respectively, compared with 9.195 ± 0.31 μg/mL for ascorbic acid. Although In(III)ClPc (4) showed the strongest activity among the phthalocyanine derivatives, all three complexes exhibited substantially weaker activity than the reference antioxidant. These differences among the complexes suggest a possible influence of the central metal ion on ABTS radical scavenging activity. Calculations of ligands and their metal complexes were performed using Gaussian software at the B3LYP, HF, and M062X levels, using the gene keyword for metal atoms Lanl2dz and other atoms in the 3-21 g basis set. Molecular docking analyses were performed against selected protein targets that are lung cancer protein (PDB ID: 4ZXT and 5ZMA), hCA I protein (PDB ID: 2CAB), hCA II protein (PDB ID: 5NN0), Escherichia coli protein (PDB ID: 1T9U), Pseudomanas aeruginosa protein (PDB ID: 3JPU), and anti-oxidant protein (Human peroxiredoxin 5) (PDB ID: 1HD2).