Guiotto A, Rodighiero P, Manzini P, Pastorini G, Bordin F, Baccichetti F, Carlassare F, Vedaldi D, Dall'Acqua F, Tamaro M
J Med Chem. 1984 Aug;27(8):959-67. doi: 10.1021/jm00374a005.
The possible presence of methylpsoralens as undesired inquinants in synthetic methylangelicins has been avoided through a synthetic pathway starting from umbelliferones carrying a methyl group in the 6-position. The new 6-methylangelicins show a high affinity toward DNA, forming in the dark a molecular complex; the complexed angelicins under UV-A irradiation photobind effectively to the macromolecule, forming only monoadducts. The new compounds show an evident antiproliferative activity by inhibiting DNA synthesis on Ehrlich cells; great differences, however, can be seen between the various compounds. All the compounds are lacking of skin erythemogenic activity. Some of the new 6-methylangelicins, evaluated in terms of mutagenic activity, demonstrate to be less effective than 8-methoxypsoralen (8-MOP), used for a comparison. On the basis of antiproliferative activity, lack of skin phototoxicity, and low mutagenicity, two compounds have been chosen for clinical evaluation. The compounds tested on seven psoriatic patients by topical application and UV-A irradiation proved to be more effective than 8-MOP, used in the same conditions.
通过从在6位带有甲基的伞形酮开始的合成途径，避免了合成甲基当归素中可能存在的甲基补骨脂素作为不良杂质的情况。新的6-甲基当归素对DNA具有高亲和力，在黑暗中形成分子复合物；在紫外线A照射下，复合的当归素有效地光结合到大分子上，仅形成单加合物。新化合物通过抑制艾氏腹水癌细胞的DNA合成显示出明显的抗增殖活性；然而，各种化合物之间存在很大差异。所有化合物均无皮肤致红斑活性。一些新的6-甲基当归素在诱变活性方面的评估表明，其效果比用作对照的8-甲氧基补骨脂素（8-MOP）差。基于抗增殖活性、无皮肤光毒性和低诱变性，选择了两种化合物进行临床评估。通过局部应用和紫外线A照射在7名银屑病患者身上测试的这些化合物被证明比在相同条件下使用的8-MOP更有效。
