Identification of Indoline-2-thione Analogs as Novel Potent Inhibitors of α-Melanocyte Stimulating Hormone Induced Melanogenesis

Abstract

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.