Thanigaimalai Pillaiyar, Lee Ki-Cheul, Sharma Vinay Kumar, Sharma Niti, Roh Eunmiri, Kim Youngsoo, Jung Sang-Hun
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, Korea.
Chem Pharm Bull (Tokyo). 2011;59(10):1285-8. doi: 10.1248/cpb.59.1285.
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.
基于筛选结果3,4-二氢喹唑啉-2-硫酮（1）和苯并咪唑-2-硫酮（2），设计、合成了一系列吲哚-2-硫酮（3）和吲哚-2-硫醇黑色素生成抑制剂（4），并在α-黑素细胞刺激激素（α-MSH）刺激下的黑色素瘤B16细胞中进行了评估。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的构效关系（SAR）研究表明，在强效抑制剂3a（30μM时抑制率>100%，IC50=1.40μM）中，3位氮（3-N）的作用不显著。此外，3的疏水取代基优于亲水取代基。然而，硫酮（-C=S，3）转化为硫醇（-C-SH，4）导致活性降低。
