410071-22-6Relevant articles and documents
Chemical insights in the concept of hybrid drugs: The antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin
Hulsman, Niels,Medema, Jan Paul,Bos, Carina,Jongejan, Aldo,Leurs, Rob,Smit, Martine J.,De Esch, Iwan J. P.,Richel, Dick,Wijtmans, Maikel
, p. 2424 - 2431 (2008/02/03)
Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory, selectively reacts with cellular GSH, which in turn triggers cell death. Remarkably, a derivative lacking ASA and the -ONO 2 group is 10 times more effective than 1. Thus, our data provide a conclusive molecular mechanism for the antitumor activity of 1. Equally importantly, we show for the first time that a "presumed invisible" linker in a hybrid drug is not so invisible after all and is in fact solely responsible for the biological effect.
Nitroderivatives as drugs for diseases having an inflammatory basis
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, (2008/06/13)
Use for the treatment of diseases having an inflammatory basis of compounds or salts thereof, having the following general formula (I): A-Xt-L-(W)p—NO2 wherein A contains the radical of a drug, Xt and W arc bivalent radicals, L, is a covalent bond or oxygen, sulphur, NRtc wherein Rtc is H or a C1-C5 linear or branched alkyl.
