Back to Journals » Drug Design, Development and Therapy » Volume 11

Design, synthesis, and antimelanogenic effects of (2-substituted phenyl-1,3-dithiolan-4-yl)methanol derivatives

Authors Kim DH, Kim SJ, Ullah S, Yun HY, Chun P, Moon HR

Received 3 January 2017

Accepted for publication 23 February 2017

Published 16 March 2017 Volume 2017:11 Pages 827—836

DOI https://doi.org/10.2147/DDDT.S131538

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rasika Samarasinghe

Peer reviewer comments 5

Editor who approved publication: Dr Sukesh Voruganti

Do Hyun Kim,1 Su Jeong Kim,1 Sultan Ullah,1 Hwi Young Yun,1 Pusoon Chun,2 Hyung Ryong Moon1

1College of Pharmacy, Pusan National University, Busan, 2College of Pharmacy, Inje University, Gimhae, South Korea

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.

Keywords: tyrosinase inhibitor, melanogenesis, 1,3-dithiolane, PDTM

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Design, synthesis, and anti-melanogenic effects of (E)-2-benzoyl-3-(substituted phenyl)acrylonitriles

Yun HY, Kim DH, Son S, Ullah S, Kim SJ, Kim YJ, Yoo JW, Jung YJ, Chun P, Moon HR

Drug Design, Development and Therapy 2015, 9:4259-4268

Published Date: 4 August 2015