Coumarin, a Lead Compound of Warfarin, Inhibits Melanogenesis via Blocking Adenylyl Cyclase

Dong-Chan Kim^1, , Seong-Hwan Rho², Dongjin Kim³, Sung In Kim¹, Chul-Soo Jang¹, Jae Ki Ryu¹, Byung Weon Kim¹, Chang Oh Kweon¹, Hyun-kyung Kim¹ and Suk Jun Lee¹

¹Department of Biomedical Laboratory Science, Gimcheon University, Gimcheon City, South Korea

²Institute for Physics, University of Freiburg, Freiburg, Germany

³School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, U.S.A

Cite this paper:
Dong-Chan Kim, Seong-Hwan Rho, Dongjin Kim, Sung In Kim, Chul-Soo Jang, Jae Ki Ryu, Byung Weon Kim, Chang Oh Kweon, Hyun-kyung Kim and Suk Jun Lee. Coumarin, a Lead Compound of Warfarin, Inhibits Melanogenesis via Blocking Adenylyl Cyclase. American Journal of Biomedical Research. 2013; 1(3):43-47. doi: 10.12691/ajbr-1-3-1

Abstract

Due to Its multiple biological activities, coumarin (a main ingredient of Cinnamon extracts) has gained attention as potentially useful therapeutics for various diseases. However, the efficacy of coumarin for the use of dermatological health has not been fully explored. To clarify the action mechanism of the skin protecting property of coumarin, we firstly investigated the molecular docking property of coumarin on the mammalian adenylyl cyclase, which is the key enzyme of cAMP-induced melanogenesis in the skin cells. In binding study, the benzopyran moiety of coumarin occupies dual sites of the hydrophobic cleft at the interface of two subunits of adenylyl cyclase. We also examined the involvement of coumarin in alpha-MSH and forskolin induced cAMP signaling within a cell based assay. In addition, we inquired into the inhibitory effect of coumarin on melanogenesis and found that the pretreatment with coumarin inhibited the forskolin-induced melanin contents significantly without annihilating the cell viability. Our results strongly suggest that coumarin directly inhibits the activity of adenylyl cyclase, downregulates forskolin-induced cAMP-production pathway, consequently inhibiting melanogenesis. Thus, coumarin may also be used as an effective inhibitor of hyperpigmentation.

Keywords:
coumarin melanin production inhibitor cyclic AMP

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