Structure-activity relationship study of 4,5-didehydroguadiscine, an aporphine alkaloid showing potent melanogenesis-inhibitory activity in B16 melanoma cells

Abstract

Although 4,5-didehydroguadiscine (12a), an alkaloid with potent melanogenesis-inhibitory activity isolated from Hornschuchia obliqua (Annonaceae), consists of an aporphine nucleus with an aromatized B-ring, to date, it has not been utilized as a template for structure–activity relationship (SAR) studies of pharmacological activities because of its exceptional structure. Accordingly, herein, five analogs (12b–12f) of 12a and five benzylisoquinoline analogs (13b–13f) lacking the C11a–C11b bond of 12b–12f were prepared. The inhibitory effects of 12b–12f and 13b–13f on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were examined and compared with those of 12a. Melanogenesis-inhibitory activities of 12b–12f were the same as that of 12a, whereas the melanogenesis-inhibitory activities of 13b–13f were significantly inferior to those of 12a and 12b–12f. These results suggest that the C11a–C11b bond plays an essential role in the melanogenesis-inhibitory activities of 12a–12e.