Synthesis and Bioevaluation of 4,5,6,7-Tetrahydrobenzo[d]isoxazole Derivatives as Melanogenesis Inhibitors

Melanin, the main component of skin color, is synthesized in the melanosomes of melanocytes through a physiological process called melanogenesis and then transferred to neigh-boring keratinocytes.1 Melanin absorbs high-energy UV radiation and transforms it into the thermal energy. In this way, melanin plays a protective role against UV-induced DNA damage.2 However, abnormal skin pigmentation is a major dermatological concern. Abnormal production of melanin causes hypopigmentation or hyperpigmentation such as vitiligo, melasma, age spot, and freckle.3 In addition, it has been reported that alteration in melanin production is observed in melanoma and Parkinson’s disease.4 Although key factors including melanocortin 1 receptor (MC1R), Microphthalmia associated transcription factor (MITF) and tyrosinase have been found, the molecular mechanism o