Palumbo M, Baccichetti F, Antonello C, Gia O, Capozzi A, Magno S M
Department of Organic Chemistry, Biopolymer Research Centre, Padova, Italy.
Photochem Photobiol. 1990 Sep;52(3):533-40. doi: 10.1111/j.1751-1097.1990.tb01796.x.
The furocoumarin derivative 3,4'-dimethyl-8-methoxypsoralen (DMe-8-MOP) exhibits remarkable antiproliferative activity, but is devoid of skin phototoxicity. To gain insight into this peculiar behaviour we investigated non-covalent and covalent binding of DMe-8-MOP to calf thymus DNA, along with DNA-synthesis inhibition and mutagenic activity. The non-covalent interaction of DMe-8-MOP with the nucleic acid is quite poor as shown by equilibrium dialysis, spectroscopic, chiroptical and hydrodynamic techniques. However, it exhibits relevant photobinding ability to DNA using both isolated nucleic acid samples and cellular systems. Unlike the large majority of congeners, DMe-8-MOP undergoes predominantly photochemical monoaddition to the double helical polynucleotide. Upon examination of the products obtained by enzymatic hydrolysis of DMe-8-MOP photomodified DNA, the formation of an unusual furan side adduct is proposed, which could account for the peculiar photochemical and photobiological properties of the 3,4'-dimethyl furocoumarin derivative.
呋喃香豆素衍生物3,4'-二甲基-8-甲氧基补骨脂素（DMe-8-MOP）具有显著的抗增殖活性，但无皮肤光毒性。为深入了解这种特殊行为，我们研究了DMe-8-MOP与小牛胸腺DNA的非共价和共价结合，以及DNA合成抑制和诱变活性。平衡透析、光谱、旋光和流体动力学技术表明，DMe-8-MOP与核酸的非共价相互作用相当弱。然而，使用分离的核酸样品和细胞系统时，它对DNA表现出相关的光结合能力。与绝大多数同类物不同，DMe-8-MOP主要对双螺旋多核苷酸进行光化学单加成。通过对DMe-8-MOP光修饰DNA的酶促水解产物进行检查，提出了一种不寻常的呋喃侧加合物的形成，这可以解释3,4'-二甲基呋喃香豆素衍生物独特的光化学和光生物学性质。
