College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6824-8. doi: 10.1016/j.bmcl.2011.09.024. Epub 2011 Sep 13.
Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in melanoma B16 cells of 1-phenylthioureas could be the result of inhibition of tyrosinase. However, 1,3-diaryl or 1-phenyl-3-alkylthioureas, 2a-k, appears as melanogenic inhibitor without inhibition of tyrosinase. The molecular docking study of 1e and 2b to binding pocket of tyrosinase provided convincing explanation regarding the necessity of direct connection of planar phenyl to thiourea unit without N'-substitution of phenylthioureas 1 as tyrosinase inhibitor and 2 as non-tyrosinase inhibitor.
我们评价了一系列 1-苯硫脲 1a-k 和 1,3-二取代硫脲 2a-k 对黑色素瘤 B16 细胞系和蘑菇酪氨酸酶中黑色素形成的影响。1-苯硫脲 1a-k 的酪氨酸酶抑制活性与其黑色素生成抑制活性平行。因此，1-苯硫脲对黑色素瘤 B16 细胞的黑色素生成抑制可能是酪氨酸酶抑制的结果。然而，1,3-二芳基或 1-苯基-3-烷基硫脲 2a-k 作为黑色素生成抑制剂而不抑制酪氨酸酶。1e 和 2b 与酪氨酸酶结合口袋的分子对接研究提供了令人信服的解释，即作为酪氨酸酶抑制剂的 1 中的苯并噻唑单元与硫脲单元之间需要直接连接，而不是 N'-取代，而 2 作为非酪氨酸酶抑制剂则不需要。
