title: 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.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, Korea.
authors.forename: Pillaiyar
authors.initials: P
authors.lastname: Thanigaimalai
authors.forename: Ki-Cheul
authors.initials: KC
authors.lastname: Lee
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Sharma
authors.forename: Niti
authors.initials: N
authors.lastname: Sharma
authors.forename: Eunmiri
authors.initials: E
authors.lastname: Roh
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008543:Melanins / Q000502:physiology*; D008546:Melanoma, Experimental / Q000378:metabolism; D058990:Molecular Targeted Therapy; D013329:Structure-Activity Relationship; D013871:Thiones / Q000737:chemistry; D000521:alpha-MSH / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D008543:Melanins; D013871:Thiones; D000521:alpha-MSH