title: Design, synthesis, and antimelanogenic effects of (2-substituted phenyl-1,3-dithiolan-4-yl)methanol derivatives.
abstract: The authors designed and synthesized 17 (2-substituted phenyl-1,3-dithiolan-4-yl) methanol (PDTM) derivatives to find a new chemical scaffold, showing excellent tyrosinase-inhibitory activity. Their tyrosinase-inhibitory activities were evaluated against mushroom tyrosinase at 50 μM, and five of the PDTM derivatives (PDTM3, PDTM7-PDTM9, and PDTM13) were found to inhibit mushroom tyrosinase more than kojic acid or arbutin, the positive controls. Of seventeen PDTMs, PDTM3 (half-maximal inhibitory concentration 13.94±1.76 μM), with a 2,4-dihydroxyphenyl moiety, exhibited greatest inhibitory effects (kojic acid half-maximal inhibitory concentration 18.86±2.14 μM). Interestingly, PDTM compounds with no hydroxyl group, PDTM7-PDTM9, also had stronger inhibitory activities than kojic acid. In silico studies of interactions between tyrosinase and the five PDTMs suggested their binding affinities were closely related to their tyrosinase-inhibitory activities. Cell-based experiments performed using B16F10 mouse-skin melanoma cells showed that PDTM3 effectively inhibited melanogenesis and cellular tyrosinase activity. A cell-viability study conducted using B16F10 cells indicated that the antimelanogenic effect of PDTM3 was not attributable to its cytotoxicity. Kinetic studies showed PDTM3 competitively inhibited tyrosinase, indicating binding to the tyrosinase-active site. We found that PDTM3 with a new chemical scaffold could be a promising candidate for skin-whitening agents, and that the 1,3-dithiolane ring could be used as a chemical scaffold for potent tyrosinase inhibition.
authors.affiliation: College of Pharmacy, Pusan National University, Busan.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan.
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan.
authors.forename: Sultan
authors.initials: S
authors.lastname: Ullah
authors.affiliation: College of Pharmacy, Pusan National University, Busan.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Inje University, Gimhae, South Korea.
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.affiliation: College of Pharmacy, Pusan National University, Busan.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
mesh_terms: D000363:Agaricales / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000432:Methanol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D014442:Monophenol Monooxygenase; D000432:Methanol
keywords: 1; 3-dithiolane; PDTM; melanogenesis; tyrosinase inhibitor