In Vitro Biological Properties of Thiazole-Containing Cobalt(II) and Copper(II) Phthalocyanines: DNA Cleavage, Antioxidant, Antimicrobial, Antibiofilm, and Surface Anti-Escherichia coli Activities

Abstract

Background/Objectives: Given the excellent biochemical and optical properties of phthalocyanines, this study aims to develop new phthalocyanine-based bioagents for multidisciplinary applications. Methods: 3-((4-(4-fluorophenyl)thiazol-2-yl)thio)phthalonitrile was synthesized by coupling 3-nitrophthalonitrile with 4-(4-fluorophenyl)thiazole-2-thiol, then cyclotetramerized in the presence of cobalt(II) or copper(II) chloride to afford phthalocyanines (TCoPc, TCuPc). Unsubstituted cobalt(II) and copper(II) phthalocyanines (CoPc, CuPc) were prepared as described in the literature and used as reference compounds. The DNA-cleavage, antioxidant, antimicrobial, antibiofilm, and surface antimicrobial activities of the new phthalocyanines were evaluated at different concentrations. The biological activities of CoPc and CuPc were investigated for the first time to examine the effects of metal ions and substituents on the phthalocyanine ring. Results: All phthalocyanines caused complete DNA degradation at 125-250 mg/L. Their antioxidant activity ranged from 16.44% to 69.54% at 6.25 mg/L and increased to 28.70-77.91% at 100 mg/L (TCuPc > TCoPc > CoPc > CuPc). TCuPc exhibited the strongest antimicrobial activity, with MIC values of 16 mg/L against S. aureus, L. pneumophila, and B. cereus, and 32 mg/L against E. hirae, P. aeruginosa, and E. coli. TCuPc also achieved the highest biofilm inhibition, up to 92.35% against S. aureus and 87.24% against P. aeruginosa at 200 mg/L, and the greatest surface antimicrobial inhibition, reaching 86.78% in the dark and 95.71% under photodynamic conditions at 50 mg/L. Conclusions: Substitution with thiazole improved the biological activities of metal phthalocyanines, and copper(II) coordination provided an additional benefit over cobalt(II). TCuPc emerges as the most promising candidate, justifying further clinical research.