Methyl derivatives of tetracyclic psoralen analogues: antiproliferative activity and interaction with DNA

被引：11

作者：

Dalla Via, L

Uriarte, E

Santana, L

Magno, SM

Gia, O ^{[1
]}

机构：

[1] Univ Padua, Dept Pharmaceut Sci, Via Marzolo 5, I-35131 Padua, Italy

[2] Univ Santiago de Compostela, Dept Organ Chem, Santiago De Compostela, Spain

来源：

ARKIVOC | 2004年

关键词：

tetracyclic psoralen analogues; antiproliferative activity; DNA interaction;

D O I：

10.3998/ark.5550190.0005.513

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A number of new tetracyclic psoralen derivatives were studied. The fourth ring is constituted by cyclopentane (4, 7 and 9), cyclohexane (11, 15 and 18) or benzene (12, 16 and 20) fused to either 4',5' or 3,4 photoreactive double bond of tricyclic furocoumarin moiety. The photoantiproliferative activity of all compounds, tested on two human tumor cell lines (HeLa and HL-60), appeared from 8 to 22 times higher than that of the well-known photochemotherapeutic drug 8-methoxypsoralen (8-MOP) in HeLa, slightly higher in HL-60. Interestingly, the evaluation of skin phototoxicity on guinea pigs evidenced a decrease in erythema induction for all compounds with respect to the drug. As regards the molecular mechanism of action, the ability to photoadd to DNA is demonstrated by isolation and characterization of the photoadducts and by the ability to give rise to interstrand cross-links for the difunctional derivatives.

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收藏

页码：131 / 146

页数：16

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