biostudies-literatureSadeghpour HShiraz University of Medical Sciences32https://www.ebi.ac.uk/biostudies/studies/S-EPMC12924469biostudies-literatureUnknown20(1)Tyrosinase is a critical rate-limiting enzyme in the melanogenesis pathway. Consequently, its inhibition represents a rational therapeutic strategy for treating skin disorders associated with excessive melanin production. In the present study, a series of novel 3-hydroxypyridine-4-one derivatives (6a-i) were synthesized, and their chemical structures were confirmed using spectroscopic techniques. The inhibitory potency of these compounds against tyrosinase was predicted using quantitative structure-activity relationship (QSAR) analysis. QSAR modeling was conducted on twenty-four previously synthesized 3-hydroxypyridin-4-one derivatives with established anti-tyrosinase activity. The best-performing model was subsequently employed to predict the IC₅₀ values of the newly synthesizeBMC chemistrySynthesis, QSAR analysis and molecular docking study of a new series of 3-hydroxypyridine-4-one derivatives as anti-tyrosinase agents.PMC1292446926571 and 25951Sadeghian SGhezeli ZKSadeghpour HRazmi PEmami LSabet RMoradian ABahrampour AKhoshneviszadeh MfalseSynthesis, QSAR analysis and molecular docking study of a new series of 3-hydroxypyridine-4-one derivatives as anti-tyrosinase agents.Tyrosinase is a critical rate-limiting enzyme in the melanogenesis pathway. Consequently, its inhibition represents a rational therapeutic strategy for treating skin disorders associated with excessive melanin production. In the present study, a series of novel 3-hydroxypyridine-4-one derivatives (6a-i) were synthesized, and their chemical structures were confirmed using spectroscopic techniques. The inhibitory potency of these compounds against tyrosinase was predicted using quantitative structure-activity relationship (QSAR) analysis. QSAR modeling was conducted on twenty-four previously synthesized 3-hydroxypyridin-4-one derivatives with established anti-tyrosinase activity. The best-performing model was subsequently employed to predict the IC₅₀ values of the newly synthesize2026-01-01T00:00:00Z2026 Jan2026-07-16T15:13:12.793Z2026-07-10T03:09:09.995ZS-EPMC129244694161240710.1186/s13065-025-01709-6