Chemical transformations of oxyresveratrol ( trans-2,4,3′,5′-tetrahydroxystilbene) into a potent tyrosinase inhibitor and a strong cytotoxic agent

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 21; pp. 5650 - 5653
• Main Authors: Likhitwitayawuid, Kittisak, Sornsute, Acom, Sritularak, Boonchoo, Ploypradith, Poonsakdi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2006; Elsevier
• Subjects: Antineoplastic agents; Biological and medical sciences; Cell Line, Tumor; Cytotoxicity; Dose-Response Relationship, Drug; General aspects; Humans; Kinetics; Medical sciences; Monophenol Monooxygenase - antagonists & inhibitors; Oxyresveratrol; Pharmacology. Drug treatments; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - toxicity; Stilbene; Stilbenes - chemistry; Stilbenes - pharmacology; Stilbenes - toxicity; Tyrosinase inhibitor; Oxyresveratrol; Cytotoxicity; Tyrosinase inhibitor; Stilbene; Antineoplastic agent; Lung; Diphenols; Etherification; Hydrogenation; Fungi; Structure activity relation; Chemical synthesis; Tumor cell; Thallophyta; Human; Ether; Enzyme; Benzene derivatives; Enzyme inhibitor; Epidermis; Monophenol monooxygenase; In vitro; Stilbene derivatives; Cell line; KB cell line; Non competitive inhibition; Oxidoreductases; Kinetics; Methylation
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.08.018

From oxyresveratrol ( trans-2,4,3′,5′-tetrahydroxystilbene 1), seven derivatives were prepared, including trans-2-methoxy-4,3′,5′-trihydroxystilbene ( 2), trans-2,3′-dimethoxy-4,5′-dihydroxystilbene ( 3), trans-4,3′-dimethoxy-2,5′-dihydroxystilbene ( 4), trans-2,4,3′,5′-tetramethoxystilbene ( 5) and cis-2,4,3′,5′-tetramethoxystilbene ( 6), 2,4,3′,5′-tetrahydroxybibenzyl ( 7), and 2,4,3′,5′-tetramethoxybibenzyl ( 8). The tetrahydroxybibenzyl 7, a hydrogenation product of 1, exhibited more potent tyrosinase inhibitory activity than the parent compound, without cytotoxicity. A kinetic study revealed that 7 was a reversible and non-competitive inhibitor of mushroom tyrosinase with l-dopa as the substrate. Analysis of the K i values indicated that 7 has a slightly higher affinity to the enzyme than 1. Compound 6, a tetra- O-methylated analogue of 1 with cis-configuration, was deprived of inhibitory effect on the enzyme tyrosinase, but showed very strong cytotoxicity against the human cancer cells KB, BC, and NCI-H187, with potency comparable to those of the anticancer agents ellipticine and doxorubicin. Data on the tyrosinase inhibitory activity and cytotoxicity of 1– 8 indicated that O methylation on stilbene 1 destroyed anti-tyrosinase activity but generated cytotoxicity. Thus, facile preparations of a potent tyrosinase inhibitor ( 7) and a strong cytotoxic agent ( 6) from the natural product 1 were achieved through simple chemical reactions.