Hydroxylated biphenyl moiety is embedded in many structures of bioactive natural products. Some of them are present in compounds of high biological relevance like ellagitannins, vancomicin, biphenomicins, others, structurally less sophisticated, are natural occurring dimers of 4-substituted 2-methoxyphenols, e.g. guaiacyl unit. In our continuing study on phenols and their C2-symmetry dimers serving as the basis for the generation of ligands for functionally and structurally discreet biological receptors1, we have prepared a small collection of natural and natural-like hydroxylated biphenyls and monomers generally bearing a guaiacyl unit as main motif. Dimers have been prepared by C-C coupling reaction with inorganic oxidizing reagents starting from the corresponding monomer or functionalized from commercial 4,4?-dihydroxybiphenyl 9. Unsaturated monomer and dimers have been prepared by Claisen-Schimdt condensation of vanillin and vanillin dimer, respectively, with the corresponding ketone. Biphenyl 9 and compound 8 are known to be in vitro inhibitors of tyrosinase, a key enzyme in melanine biosynthesis involved in determining the colour of mammalian skin and hair, in unfavorable enzymatic browning of plant-derived foods and in insects molting process. Tyrosinase inhibitory activity have been detected via spectrophotometric assay in compounds, 1, 2, 4, 7, 10, 11 and 12, structurally related to 9 and 8, and in insects molting trial. Viability (80%) of compounds 1, 2, 4, 7, 8 and 10 in PC12 cells, a neuronal cell model, have been observed at concentration > 10 uM. In order to improve the biological activity of the guaiacyl unit present in phenols and C2-dimers1, we have planned to introduce a ferrocene unit because of the promising results observed in medicinal field when a metallocene moiety is embedded with bioactive compounds. Their electrochemical potential and cytotoxic activity in PC12 cells have been evaluated in comparison with data of the corresponding compounds lacking in ferrocene unit. All ferrocenylchalcones showed a reversible behavior, but not the saturated analog of compound 6.
HYDROXYLATED PHENOLS AND DIMERS: A VALUABLE SOURCE OF BIOACTIVE COMPOUNDS
FABBRI D;DETTORI M A;PATTI A;PEDOTTI S;BARBERIS A;RUZZA P;CARTA P;
2014
Abstract
Hydroxylated biphenyl moiety is embedded in many structures of bioactive natural products. Some of them are present in compounds of high biological relevance like ellagitannins, vancomicin, biphenomicins, others, structurally less sophisticated, are natural occurring dimers of 4-substituted 2-methoxyphenols, e.g. guaiacyl unit. In our continuing study on phenols and their C2-symmetry dimers serving as the basis for the generation of ligands for functionally and structurally discreet biological receptors1, we have prepared a small collection of natural and natural-like hydroxylated biphenyls and monomers generally bearing a guaiacyl unit as main motif. Dimers have been prepared by C-C coupling reaction with inorganic oxidizing reagents starting from the corresponding monomer or functionalized from commercial 4,4?-dihydroxybiphenyl 9. Unsaturated monomer and dimers have been prepared by Claisen-Schimdt condensation of vanillin and vanillin dimer, respectively, with the corresponding ketone. Biphenyl 9 and compound 8 are known to be in vitro inhibitors of tyrosinase, a key enzyme in melanine biosynthesis involved in determining the colour of mammalian skin and hair, in unfavorable enzymatic browning of plant-derived foods and in insects molting process. Tyrosinase inhibitory activity have been detected via spectrophotometric assay in compounds, 1, 2, 4, 7, 10, 11 and 12, structurally related to 9 and 8, and in insects molting trial. Viability (80%) of compounds 1, 2, 4, 7, 8 and 10 in PC12 cells, a neuronal cell model, have been observed at concentration > 10 uM. In order to improve the biological activity of the guaiacyl unit present in phenols and C2-dimers1, we have planned to introduce a ferrocene unit because of the promising results observed in medicinal field when a metallocene moiety is embedded with bioactive compounds. Their electrochemical potential and cytotoxic activity in PC12 cells have been evaluated in comparison with data of the corresponding compounds lacking in ferrocene unit. All ferrocenylchalcones showed a reversible behavior, but not the saturated analog of compound 6.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
