Solid-phase synthesis of a combinatorial methylated (±)-epigallocatechin gallate library and the growth-inhibitory effects of these compounds on melanoma B16 cells.
We report on the solid-phase synthesis of a combinatorial methylated (±)-epigallocatechin gallate (EGCG) library and its biological evaluation. Epigallocatechin gallate (EGCG) and its methylated derivatives, which are members of the catechin family, exhibit various anti-cancer effects. The solid-phase synthesis of methylated EGCG involves the preparation of the α-acyloxyketone by the coupling of a solid-supported aldehyde with a ketone and an acid. The subsequent release and reductive etherification reaction of the solid-supported α-acyloxyketone provide the protected EGCG in good total yields. Sixty-four methylated EGCGs were successfully prepared. The growth-inhibitory effects of the methylated EGCG library were also examined. Although methylation of EGCG generally causes reduced growth inhibition, the growth-inhibitory effect of 7-OMe EGCGs was comparable to that of EGCG. The 7-OMe EGCGs are attractive drug candidates because of their enhanced bioavailability.
Tanaka
Hiroshi
H
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan. thiroshi@apc.titech.ac.jp
Yamanouchi
Maasa
M
Miyoshi
Haruko
H
Hirotsu
Keisuke
K
Tachibana
Hirofumi
H
Takahashi
Takashi
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D006865:Hydrogenation; D008546:Melanoma, Experimental / Q000188:drug therapy; D008745:Methylation; D051379:Mice; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity
D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D002392:Catechin; C045651:epigallocatechin gallate