The molecular structure of 1,4,6,8-tetramethylfuro[2,3-h]quinolin-2(1H)-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(1H)-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 (DPCL>0) was replaced by an efficient production of DNA–protein cross-links at zero length (DPCL=0), probably via guanine damage. Because of its angular molecular structure, HOFQ does not form interstrand cross-links (ISC): therefore, DPCL=0 and MA represent the main lesions induced by HOFQ in DNA. In comparison with FQ (which induces MA and DPCL>0) and 8-methoxypsoralen (8-MOP) (MA, ISC, DPCL>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.
You have requested a machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Neither BioOne nor the owners and publishers of the content make, and they explicitly disclaim, any express or implied representations or warranties of any kind, including, without limitation, representations and warranties as to the functionality of the translation feature or the accuracy or completeness of the translations.
Translations are not retained in our system. Your use of this feature and the translations is subject to all use restrictions contained in the Terms and Conditions of Use of the BioOne website.
Vol. 81 • No. 6