Dall'Acqua F, Vedaldi D, Bordin F, Baccichetti F, Carlassare F, Tamaro M, Rodighiero P, Pastorini G, Guiotto A, Recchia G, Cristofolini M
J Med Chem. 1983 Jun;26(6):870-6. doi: 10.1021/jm00360a016.
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.
制备了当归素（1）的三种衍生物[4'-甲基-、4,4'-二甲基-和4',5-二甲基当归素（2a - c）]，目的是获得用于银屑病光化学疗法的新药物。这些化合物在黑暗中与DNA形成复合物，该复合物对大分子的亲和力高于母体当归素（1）。已观察到它们的辛醇/水分配系数与复合物的缔合常数之间存在相关性。化合物2a - c与DNA的光结合程度比1高得多，也比作为参考化合物的8-甲氧基补骨脂素（8-MOP）更有效。当用UV-A激活时，这三种化合物能强烈使T2噬菌体失活并抑制小鼠表皮DNA合成。此外，它们对大肠杆菌野生型菌株的诱变活性明显低于8-甲氧基补骨脂素。由于其缺乏皮肤光毒性、低诱变活性和抗增殖活性，选择2c进行临床评估。事实证明，它对两名患者的银屑病清除有效。
