Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30 µM, IC50=1.40 µM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.

中文翻译：

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确认吲哚啉-2-硫酮类似物是α-黑素细胞刺激激素诱导的黑色素生成的新型有效抑制剂。

根据命中率，3,4-二氢喹唑啉-2-硫酮（1）和苯并咪唑-2-硫酮（2），一系列的吲哚-2-硫酮（3）和吲哚-2-硫醇抑制剂（4）在α-黑素细胞刺激激素（α-MSH）的刺激下，在黑素瘤B16细胞中进行了设计，合成和评估。吲哚-2-硫酮化合物（3a-g）对黑色素合成表现出有效的抑制活性。对2的结构-活性关系（SAR）研究表明，在有效的抑制剂3a中（在30 µM时抑制率大于100％，IC50 = 1.40 µM），在3位上的氮（3-N）作用微不足道。另外，3的疏水取代基优于亲水的取代基。然而，硫酮（-C = S，3）向硫醇（-C-SH，4）的转化导致效力降低。