J. Cosmet. Sci., 65, 175–186 (May/June 2014) 175 Effect of novel cyclohexane diester and benzene diester derivatives on melanogenesis JONG WOO CHEON, JI MIN JEON, MOON JEONG CHOI, SI JUN PARK, and SANG YO BYUN, R&D Center, ACT Co., Ltd., 486 Sin-dong (J.W.C., J.M.J., M.J.C., S.J.P.), Suwon, Republic of Korea and Cosmetic Science Major, Department of Applied Biotechnology, Ajou University, Woncheon-dong (J.W.C., S.Y.B.), Suwon 443-749, Republic of Korea. Accepted for publication March 20, 2014. Synopsis In order to investigate potent whitening agents, we synthesized 15 cyclohexane diester derivatives and 15 ben- zene diester derivatives. To evaluate their structure–cytotoxicity relationships, we performed cell cytotoxicity tests on B16F10 mouse melanoma cells. To understand their whitening effects, melanin synthesis inhibitory activities in B16F10 cells and mushroom tyrosinase inhibitory activities were performed. In most cases, cell cytotoxicity was observed to be lower in 1,3-diester than in 1,2- and 1,4-diesters when it came to the structural isomer of the side chain, all derivatives except the 1,2-cyclohexane diester derivatives showed lower cell cyto toxicity in the branch type of the side chain than in the linear type. Among the compounds evaluated, the compounds cyclohexane-1,3-diyl bis(decanoate), cyclohexane-1,4-diyl dioctanoate, and 1,3-phenylene bis (2-ethylhexanoate) emerged as potent melanin synthesis inhibitors. Our goal was to determine the expression levels of proteins involved in melanogenesis, Western blotting and RT-PCR showing that these compounds decreased tyrosinase, TRP-1, and TRP-2 while demonstrating signifi cantly low cytotoxicity. INTRODUCTION Melanin is a major pigment produced by melanocyte cells in the basal layer of human skin and overproduced by chronic sun exposure or other hyperpigmentation diseases (1). Melanin synthesis is regulated by the rate-limiting enzyme of tyrosinase, which is a membrane-bound copper containing glycoprotein that initiates the biosynthetic pathway of melanin by catalyzing the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA). Subsequent reactions in the melanin synthetic pathway—for example, the con- version of DOPA to DOPAquinone as well as other non-enzymatic reactions—are oxida- tive reactions (2). Tyrosinase is known to be a key enzyme for melanin biosynthesis in plants, microorganisms, and human cells. Against this backdrop, many tyrosinase in- hibitors have been tested in cosmetics and pharmaceuticals as a way of preventing any overproduction of melanin in epidermal layers (3). Address all correspondence to Jong Woo Cheon at actcjw@actcos.com.