title: Comparison of a pair of synthetic tea-catechin-derived epimers: synthesis, antifolate activity, and tyrosinase-mediated activation in melanoma.
abstract: Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin-derived compounds, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), in an attempt to improve the stability and cellular absorption of tea polyphenols. The antiproliferative and pro-apoptotic activities of both compounds were analyzed with various cancer cell systems, and TMCG, which was easily synthesized in excellent yield, was more active than TMECG in both melanoma and non-melanoma cell lines. TMCG was also a better inhibitor of dihydrofolate reductase and was more efficiently oxidized by tyrosinase, potentially explaining the difference in activity between these epimers.
authors.affiliation: Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, and REsearch Unit of Clinical Analysis Service, University Hospital Virgen de la Arrixaca, Avda. Teniente Flomesta, no. 5, 30003 Murcia, Spain.
authors.forename: Magalí
authors.initials: M
authors.lastname: Sáez-Ayala
authors.forename: Luis
authors.initials: L
authors.lastname: Sánchez-del-Campo
authors.forename: María F
authors.initials: MF
authors.lastname: Montenegro
authors.forename: Soledad
authors.initials: S
authors.lastname: Chazarra
authors.forename: Alberto
authors.initials: A
authors.lastname: Tárraga
authors.forename: Juan
authors.initials: J
authors.lastname: Cabezas-Herrera
authors.forename: José Neptuno
authors.initials: JN
authors.lastname: Rodríguez-López
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008545:Melanoma / Q000188:drug therapy*; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013662:Tea / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism
chemical_list: C559677:3-O-(3,4,5-trimethoxybenzoyl)catechin; C529447:3-O-(3,4,5-trimethoxybenzoyl)epicatechin; D000970:Antineoplastic Agents; D000975:Antioxidants; D005493:Folic Acid Antagonists; D013662:Tea; D002392:Catechin; D014442:Monophenol Monooxygenase; D013762:Tetrahydrofolate Dehydrogenase