Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1358, 2026 (SCI-Expanded, Scopus)
Since irregular skin pigmentation can trigger various diseases and is also considered an aesthetic concern, there is a growing demand for effective melanogenesis inhibitors. Tyrosinase, the key enzyme in the melanogenesis pathway, plays a central role in the treatment of hyperpigmentation by catalyzing the first and rate-limiting step of melanin biosynthesis. Although natural compounds are often preferred as tyrosinase inhibitors, their limited chemical stability and insufficient solubility have increased interest in synthetic inhibitors. The aim of this study was to design, synthesis and investigate the biological activity of the first cyclotriphosphazene-based tyrosinase inhibitor. In context, thiophene and thiomorpholine derivatives of cyclotriphosphazene (2–6) were synthesized, purified and structurally characterized using mass and NMR (31P, 1H and 13C) techniques. The expected planar orientation of the cyclotriphosphazene core was confirmed by X-ray crystallographic analysis of compounds 4 and 5. The inhibitory activities of these compounds against tyrosinase were evaluated using in vitro and in silico approaches, and their pharmacokinetic properties were also assessed. Among the tested compounds, compound 2 exhibited the strongest inhibitory activity, with an IC₅₀ value of 0.083±0.000 mM (p<0.05). All of the compounds exhibited good radical scavenging and antibacterial activity. Overall, these findings indicate that the cyclotriphosphazene scaffold represents a promising building block for the design and synthesis of novel melanogenesis enzyme inhibitors.