Structural requirements of (E)-6-benzylidene-4a-methyl-4,4a,5,6,7,8- hexahydronaphthalen-2(3H)-one derivatives as novel melanogenesis inhibitors

Chalcone type compound 1a ((E)-6′-benzylidene-4a′-methyl- 4′,4a′,7′,8′-tetrahydro-3′H-spiro[[1,3] dithiolane-2,2′-naphthalen]-5′(6′H)-one) was discovered as an potent inhibitor in melanogenesis. To define its structure-activity relationship, a series of analogs 1b-n, dithiolane truncated 2a-b and ring A removed 3a-e were prepared and evaluated. The electron donating substitution on the phenyl ring (ring C) rather than an electron withdrawing group and dithiolane motif of 1 are needed for the activity enhancement. The scaffold containing both rings A and B associated with α,β-unsaturated system connected to phenyl of 1 was essential for antimelanogenesis.