In:
Photochemistry and Photobiology, Wiley, Vol. 81, No. 6 ( 2005-11), p. 1371-1379
Abstract:
The molecular structure of 1,4,6,8‐tetramethylfuro[2,3‐ h ]quinolin‐2(1 H )‐one (FQ), a recent furocoumarin‐like photosensitizer, has been modified with the aim of reducing its strong genotoxicity, by replacing the methyl group at 4 position with a hydroxymethyl one, and so obtaining 4‐hydroxymethyl‐1,6,8‐trimethylfuro[2,3‐ h ]quinolin‐2(1 H )‐one (HOFQ). This modification gave rise to a strong reduction of lipophilicity and dark interaction with DNA. The formation of monoadducts (MA) was deeply affected, whereas the induction of bifunctional adducts between DNA and proteins (DPC L 〉 0 ) was replaced by an efficient production of DNA–protein cross‐links at zero length (DPC L =0 ), probably via guanine damage. Because of its angular molecular structure, HOFQ does not form interstrand cross‐links (ISC): therefore, DPC L 〉 0 and MA represent the main lesions induced by HOFQ in DNA. In comparison with FQ (which induces MA and DPC L 〉 0 ) and 8‐methoxypsoralen (8‐MOP) (MA, ISC, DPC L 〉 0 ), HOFQ seems to be a more selective agent. In fact, contrary to FQ and 8‐MOP, HOFQ, together with a noticeable antiproliferative activity, shows low levels of point mutations in bacteria and of clastogenic effects in mammalian cells. HOFQ is also an efficient apoptosis inducer, especially in comparison with 8‐MOP, when tested at equitoxic experimental conditions; this property might be correlated with the complete HOFQ inability of inducing skin erythemas, a well‐known side effect of classic furocoumarin photosensitization.
Type of Medium:
Online Resource
ISSN:
0031-8655
,
1751-1097
DOI:
10.1562/2005-01-13-RA-413
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2048860-9
SSG:
12
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