密花香薷的化学成分

从密花香薷 (Elsholtzia densa Benth.)中分得 10个化合物 ,经波谱分析和化学方法鉴定为 :二十九碳烷 (1)、丁二酸 (2 )、5- (3″,3″-二甲基烯丙基 ) - 8-甲氧基呋喃香豆素 (3)、5- (3″-甲基丁基 ) - 8-甲氧基呋喃香豆素 (4)、5- (3″-羟基 - 3″-甲基丁基 ) - 8-甲氧基呋喃香豆素 (5)、3,4-二羟基肉桂酸 (6)、5-羟基 - 3′-甲氧基双氢黄酮 - 7- O-芸香糖甙 (7)、槲皮素 - 3- O- β- D-葡萄糖甙 (8)、山奈素 - 3- O- β- D-葡萄糖甙 (9)、5-羟基 - 4′-甲氧基黄酮 - 7- O-芸香糖甙 (10 )。其中 ,化合物 4和 5是新的天然产呋喃香豆素。     

Synthesis and biological evaluation of furocoumarin derivatives on melanin synthesis in murine B16 cells for the treatment of vitiligo

Furocoumarins, isolated from Psoralen corylifolia L., were found to be the most effective drug in the treatment of vitiligo nowadays. Twenty-five furocoumarin derivatives were thus designed and synthesized in order to improve the melanogenesis in B16 cells for the first time. Among them, twenty-three compounds were more potent than the positive control (8-MOP), the commonly used drug for vitiligo in clinic. Noticeably, compounds 6m (350.5%) and 6p (313.1%) based on the scaffold of 6k (2H-benzofuro[2,3-h]chromen-2-one) were nearly 3-fold stronger than 8-MOP (114.50%). The in vitro melanin synthesis evaluation of these structurally diverse analogues had also led to an outline of structure–activity relationship.     

The Chemical Constituents of Elsholtzia densa Benth.

Ten compounds were isolated from Elsholtzia densa Benth. and their structures were identified by spectral and chemical methods as following: n-nonacosane (1), succinic acid (2), 5- ( 3 ”, 3 ”-dimethylallyl ) -8-methoxyfurocoumarin (3), 5- ( 3 ”-methylbutyl) -8- methoxyfurocoumarin (4), 5- (3”-hydroxy-3”-methylbutyl) -8-methoxyfurocoumarin (5), 3, 4-dihydroxycinnamic acid ( 6 ), 5-hydroxy-3’-methoxyflavanone-7-O-rutinoside ( 7 ), quercetin-3-O-β-D-glucoside ( 8 ), kaempferol-3-O-β-D-glucoside ( 9 ), 5-hydroxy-4’- methoxyflavone-7-O-rutinoside (10). Among them, compounds 4 and 5 are new naturally occurring furocoumarins.     

Cinnamic acid 4-hydroxylase mechanism-based inactivation by psoralen derivatives: cloning and characterization of a C4H from a psoralen producing plant-Ruta graveolens-exhibiting low sensitivity to psoralen inactivation

Cinnamate 4-hydroxylase (C4H, EC 1.14.13.11) complete cDNA was cloned from the leaves of Ruta graveolens, a psoralen producing plant. The recombinant enzyme (classified CYP73A32) was expressed in Saccharomyces cerevisiae. Mechanism-based inactivation was investigated using various psoralen derivatives. Only psoralen and 8-methoxypsoralen were found to inactivate C4H. The inactivation was dependent on the presence of NADPH, time of pre-incubation, and inhibitor concentration. Inactivation stoichiometry was 0.9 (+/-0.2) for CYP73A1 and 1.1 (+/-0.2) for CYP73A32. SDS-PAGE analysis demonstrated that [3H]psoralen was irreversibly bound to the C4H apoprotein. K(i) and k(inact) for psoralen and 8-methoxypsoralen inactivation on the two C4H revealed a lower sensitivity for CYP73A32 compared to CYP73A1. Inactivation kinetics were also determined for CYP73A10, a C4H from another furocoumarin-producing plant, Petroselinum crispum. This enzyme was found to behave like CYP73A32, with a weak sensitivity to psoralen and 8-MOP inactivation. Cinnamic acid hydroxylation is a key step in the biosynthesis of phenylpropanoid compounds, psoralen derivatives included. Our results suggest a possible evolution of R. graveolens and P. crispum C4H that might tolerate substantial levels of psoralen derivatives in the cytoplasmic compartment without a depletive effect on C4H and the general phenylpropanoid metabolism.     

Penetration and localization of furocoumarins in single living cells studied by microspectrofluorometry

The microspectrofluorometric technique has been used to study the penetration and the localization of psoralen, 4,5′,8-trimethylpsoralen and 4′-aminomethyltrioxsalen in single living L-cells. The concentration of the different compounds inside the cell reached a plateau in 2 min with psoralen and aminomethyltrioxsalen and in 20 min with trioxsalen. Washing of the cells with culture medium produced only a partial removal of the three furocoumarins, distributed apparently in equivalent amount in the nucleus and cytoplasm.