4'-Methylangelicins: new potential agents for the photochemotherapy of psoriasis.
Three derivatives of angelicin (1) [4'-methyl-, 4,4'-dimethyl-, and 4',5-dimethylangelicin (2a-c)] have been prepared with the aim of obtaining new agents for the photochemotherapy of psoriasis. These compounds form a complex in the dark with DNA that shows an affinity for the macromolecule higher than that of the parent angelicin (1). A correlation between their octanol/water partition coefficients and the association constants of the complexes has been observed. Compounds 2a-c photobind to DNA to a much higher extent than 1 and also more effectively than 8-methoxypsoralen (8-MOP), taken as reference compound. When activated with UV-A, the three compounds strongly inactivate T2 phage and inhibit epidermal DNA synthesis in mice. Moreover, they show a mutagenic activity markedly lower than that of 8-methoxypsoralen on Escherichia coli wild-type strain. Due to its lack of skin phototoxicity, its low mutagenic activity, and its antiproliferative activity, 2c was chosen for clinical evaluation. It proved to be effective in clearing psoriasis in two patients.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects; D011564:Furocoumarins / Q000138:chemical synthesis / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D009152:Mutagenicity Tests; D010789:Phototherapy; D011565:Psoriasis / Q000628:therapy*; D012995:Solubility; D013604:T-Phages / Q000187:drug effects
D011564:Furocoumarins; C038161:4,4'-dimethylangelicin; C038162:4',5-dimethylangelicin; C038163:4'-methylangelicin; D004247:DNA