Furanocoumarin derivatives

Mohri K, Uesawa Y. Effects of furanocoumarin derivatives in grapefruit juice on nifedipine pharmacokinetics in rats. Pharm Res 2001 18(2) 177-182. 

Ohnishi A, Matsuo H, Yamada S, et al. Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4. Br J Pharmacol 2000 130(6) 1369-1377. 

Guo LQ, Fukuda K, Ohta T, Yamazoe Y. Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos 2000 28(7) 766-771. 

Psoralens, e.g., 8-methoxypsoralen, are a family of furanocoumarin derivatives that have been used in part to treat diseases such as psoriasis and cutaneous... 

The furanocoumarin derivative, 5-methoxypsoralen, and other related compounds, are responsible for the phototoxicity of various essential oils on skin (9, 65, 169). Other studies with lapachol concern its toxicity to viruses (98) and parasites (102). The sensitizing capacity of naphthoquinones was studied on guinea pigs (166). The problem of photosensitization was present in livestock (93). The effects were caused by 5-methoxypsoralen, and also the bis-anthraquinone hypericin. The flavanoids are thought to be responsible for a contact eczema from Robinia sp. (190). 

The cutaneous phototoxicity of a-terthienyl was studied in guinea pig skin, both in vitro and in vivo 203). Effective penetration through the epidermis and superficial dermis produced cutaneous photosensitization comparable to that of intradermally administered a-terthienyl. Phototoxicity was accompanied by a corresponding inhibition of epidermal DNA synthesis in normal and hyperproliferative skin. The authors suggested that a-terthienyl might provide a selective and safer alternative to coal tar and furanocoumarin derivatives for the treatment of psoriasis and other cutaneous diseases by photosensitization. However, no clinical studies in this direction have yet been published. 

The phthalide derivatives cnidilide, (.Z)-ligustilide, (3>S )-butylphtha-lide, neocnidilide, and Z-butyldienepthaHde and the furanocoumarins xanthotoxin and isopimpinellin have been reported as insecticides and... 

Hadacek F, Mueller C, Werner A, Greger H, Proksch P, Analysis, isolation and insecticidal activity of linear furanocoumarins and other coumarin derivatives from Peuxedanum (Apiaceae Apioideae),/ Ecol 20 2035—2054, 1994. 

Many if not most furanocoumarln derivatives possess potent photoactive properties. It is generally accepted that the biological actions of furanocoumarins are attributable to the fact that these compounds easily intercalate into the double helix of DNA, where they produce cyclobutane adducts with... 

Although the CNB hypothesis predicts changes in concentrations in all C-based secondary metabolites in relation to the plant C/N status, different classes of these metabolites may respond differently to environmental variation,175 176 since they are derived from different biosynthetic pathways, represent different proportions of a plant s carbon budget, and may have different turnover rates.8 176 177 Early successional herbs and woody plants that produce phenolic compounds conform to the CNB hypothesis178 more predictably than plants that produce other classes of C-based secondary metabolites such as terpenes176 179 and furanocoumarins.180... 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

The main degradation path of 2-formylbenzofuran (21) is explained by loss of two molecules of CO, forming possibly a benzocyclopropene ion,26 (21)->[22] [23], which can lose a hydrogen atom to give a fragment of mass 89, thought to be a dehydrotropylium ion [24], which is also found in the spectra of other benzofuran derivatives,226 coumarin,24 and furanocoumarins.27,28... 

Extensive studies by Brov/n continue to elucidate the pathways to the furanocoumarins in various plants. Marmesin (13) and columbianetin (14) are still the only coumarin precursors of the furanocoumarins to retain a whole iso-prenoid unit. The related chromone derivative visamminol (15) is presumably a precursor of the furanochromone visnagin. Full details have appeared on the specific incorporation of mevalonate into the furan ring of skimmi-anine (16). 

Furochromones are group of coumarins, derived from y- benzopyrone. They are related to furanocoumarins and are present in plants of family Apiaeeae and Rutaceae. Ammi visnaga is a potential souree of furoehromones like khellin and visnagin. Khellin was onee used as coronary vasodilator drug. 

Furanocoumarin and Furanoquinoline Derivatives.—The two extra carbon atoms of these furanoid rings are derived from C 4,5 of mevalonic acid. Probably very similar processes occur in both types of secondary metabolites. For ex-ample, psoralen (21 R = H) and bergapten (21 R = OH) are derived from umbelliferone (18) via marmesin (19) and their dihydro-derivatives (20). An... 

In coumarin itself all ]J(C,H)-values are within a small range (about 163-165.5 Hz) except for C-3, which has the only value larger than 170 Hz. This was used to differentiate between C-3 and C-8 (21). The same pattern was found for a variety of derivatives for example, it was helpful in assigning C-3 and C-6 in some aminocoumarins (28) only for coumarins bearing a 4-hydroxy group is J(C-3,H-3) considerably smaller (15, 19, 24). In furanocoumarins, the largest J(C,H)-values appear in the furan moiety, that for C-2 even exceeding 200 Hz (23, 26, 27, 31, 32). 

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