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245 1 0 _aChemical transformations of oxyresveratrol (trans-2,4,30,50-tetrahydroxystilbene)into a potent tyrosinase inhibitor and a strong cytotoxic agent
490 0 _vBioorganic & Medicinal Chemistry Letters, 16(21), p.5650-5653, 2006
520 3 _aFrom oxyresveratrol (trans-2,4,30,50-tetrahydroxystilbene 1), seven derivatives were prepared, including trans-2-methoxy- 4,30,50-trihydroxystilbene (2), trans-2,30-dimethoxy-4,50-dihydroxystilbene (3), trans-4,30-dimethoxy-2,50-dihydroxystilbene (4), trans-2,4,30,50-tetramethoxystilbene (5)and cis-2,4,30,50-tetramethoxystilbene (6), 2,4,30,50-tetrahydroxybibenzyl (7), and 2,4,30,50- 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 Ki 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.
700 1 2 _aLikhitwitayawuid, K.
700 1 2 _aSornsute, A.
856 4 0 _uhttps://drive.google.com/file/d/1rUTRNdZIjPQU0mWwdpbpNyL9zO9ypMxM/view?usp=drivesdk
_zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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