Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

Chem Pharm Bull (Tokyo). 2011;59(10):1285-8. doi: 10.1248/cpb.59.1285.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Design
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • Indoles / chemistry
  • Inhibitory Concentration 50
  • Melanins / physiology*
  • Melanoma, Experimental / metabolism
  • Molecular Targeted Therapy
  • Structure-Activity Relationship
  • Thiones / chemistry
  • alpha-MSH / antagonists & inhibitors*

Substances

  • Indoles
  • Melanins
  • Thiones
  • alpha-MSH