This technology is a pharmaceutical composition for the prevention and treatment of uveal melanoma, containing 5-demethoxy-5-methyl-7-chloro-melatonin or 7-bromo-melatonin, in which chlorine or bromine is introduced into the melatonin backbone, as an active ingredient. It also includes food products for the improvement and prevention of uveal melanoma containing the same compounds, which are obtained through enzymatic conversion using flavin-dependent halogenase derived from Micromonospora actinomycetes.
While melatonin and some of its metabolites have been reported to inhibit the growth of metastatic uveal melanoma cells—a type of eye cancer—beyond their role in sleep regulation, they have been difficult to use as therapeutic agents due to their extremely short half-life and low oral bioavailability. Furthermore, chemical halogenation requires toxic reagents and harsh reaction conditions, and results in mixtures of isomers and by-products, limiting the development of new halogenated melatonin derivatives.
This technology utilizes a highly site-specific enzymatic reaction to attach halogens to specific positions on melatonin-like indole compounds, resulting in novel derivatives with improved melatonin receptor binding affinity and anti-tumor activity against uveal melanoma cells. The eco-friendly biocatalytic process also minimizes by-products. It can be applied to new drugs for rare eye cancers like uveal melanoma, adjuvant therapies for ocular tumors, and melatonin-based functional food ingredients, providing new small-molecule candidates for a field with limited treatment options.
This invention was developed with support from the Rural Development Administration for the production of novel glycosylated antibiotics utilizing soil actinomycete genetic resources based on biosynthetic pathway engineering.
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