4‘-Methyl Derivatives of 5-MOP and 5-MOA:  Synthesis, Photoreactivity, and Photobiological Activity

Abstract

The synthesis and photobiological activity of four new 4'-methyl derivatives of 5-MOP (5-methoxypsoralen) and 5-MOA (5-methoxyangelicin), i.e., 4,4'-dimethyl-5-methoxypsoralen, 3,4'-dimethyl-5-methoxypsoralen, 4,4'-dimethyl-5-methoxyangelicin, and 3,4'-dimethyl-5-methoxyangelicin, are described. All these compounds photobind efficiently to DNA. The DNA-photobinding process was investigated using various nucleic acid structures such as double-helix DNA, bacterial DNA, and synthetic polydeoxyribonucleotides. Photoreaction experiments showed that, unlike 8-MOP (8-methoxypsoralen) and 5-MOP, both angular derivatives bind thymine and cytosine with the same efficiency. The principal nucleoside-psoralen monoadducts were isolated and characterized after enzymatic digestion or acid hydrolysis. Biological activity studies revealed a good correlation with the extent of covalent photoaddition. Moreover, the two angular derivatives and the 4,4'-dimethyl-5-methoxypsoralen were unable to induce skin erythema, in striking contrast with the reference drugs, 8-MOP and 5-MOP; only the 3,4'-dimethyl-5-methoxypsoralen caused erythema, although to a substantially lower extent than that induced by the two parent compounds.

Effects of psoralens as anti-tumoral agents in breast cancer cells

“…Psoralens, extremely toxic to a wide variety of prokaryotic and eukaryotic organisms, are mainly extracted from the ripe fruit of Psoralea corylifolia (Leguminosae), an erect annual herb widely used in Ayurvedic medicine and traditional Chinese medicine. 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), or bergapten, are the psoralen compounds that occur in nature but several analogues have also been described [15][16][17][18][19][20] . These molecules cause cell damage by covalent binding to DNA after ultraviolet radiation A (UVA) irradiation.…”

Furocoumarins in Medicinal Chemistry. Synthesis, Natural Occurrence and Biological Activity

“…Alternatively, a modification of this method employing microwaves in the absence of solvent [14] can also be used to obtain the same products. These intermediates undergo a cyclization reaction to provide the desired furocoumarins with acceptable yields [15][16][17][18] (Scheme 1).…”

3-Alkyl- and 3-Aryl-7H-furo[3, 2-g]-1-benzopyran-7-ones: Synthesis, Photoreactivity, and Fluorescence Properties

“…Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker ARX 300 MHz FT NMR spectrometer, and chemical shifts (ppm) are reported relative to tetramethylsilane as internal standard in CDCl 3 or in DMSO-d 6 or the solvents peak (CDCl 3 7.24 ppm, DMSO-d 6 .The absorbance spectra were recorded with a HP 8845A diode-array spectrophotometer fitted with a Julabo F20-C heating controller. Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker ARX 300 MHz FT NMR spectrometer, and chemical shifts (ppm) are reported relative to tetramethylsilane as internal standard in CDCl 3 or in DMSO-d 6 or the solvents peak (CDCl 3 7.24 ppm, DMSO-d 6 .The absorbance spectra were recorded with a HP 8845A diode-array spectrophotometer fitted with a Julabo F20-C heating controller.…”

“…Furocoumarins also react with proteins and membrane lipids, either by direct photoaddition or by generation of singlet oxygen, which suggests that parallel to the DNA reaction other cellular targets should be taken into account when attempting to explain furocoumarin photosensitization [14]. This method has been used by several groups for measuring the generation of singlet oxygen [6,10,[15][16][17][18][19]. The author was interested in the preparation and investigation of furocoumarins which have hydrophobic and bulky substituents on the furan moiety, in order to check the influence of the structural changes in position 3 of the furocoumarin skeleton on the interaction with DNA as well as on the absorption and fluorescence spectra, the lipophilicity, and the photobleaching effect of N,N-dimethyl-p-nitrosoaniline.…”