Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC₅₀ value of 0.46 and 0.50 µM, respectively. In kinetic evaluation against TYR, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure-activity relationship analysis.

黑色素和黑色素生成是一把双刃剑。黑色素具有辐射防护作用，而黑色素生成具有不良影响。针对黑色素生成途径，设计、合成了一系列与不同喹唑啉酮衍生物结合的 kojyl 硫醚，并评估了它们对蘑菇酪氨酸酶的抑制活性。筛选所有合成化合物的抗酪氨酸酶活性，所有衍生物均显示出比曲酸更好的效力，作为阳性对照。在这方面，5j和5h作为最活跃的化合物，其 IC ₅₀值分别为 0.46 和 0.50 µM。在针对 TYR 的动力学评估中，5j描绘了一种非竞争性的抑制模式。设计的化合物还表现出温和的抗氧化能力。此外，5j和5h对 B16F10 细胞系具有良好的效力，以减少黑色素含量，同时对恶性细胞显示出有限的毒性。通过分子对接评估的新抑制剂的拟议结合模式与构效关系分析的结果一致。