Evaluation of the NO-releasing properties of NO-donor linkers.
This work describes the synthesis of some benzoic (1-4) and alcoholic (5-7) nitrooxy derivatives, which are nitric oxide (NO) donors in themselves, and can also be seen as useful linkers that can be used in multi-target drugs capable of releasing NO. The NO-mediated vasorelaxing effects of the compounds were tested on endothelium-denuded isolated rat aortic rings pre-contracted with KCl. The pharmacological study of these compounds demonstrated that slight structural modification, such as the insertion of (a) methyl group(s) into the nitrooxymethyl chain or into the aromatic ring, and a change in the position of this nitrooxymethyl chain, could exert a marked (and potentially useful) influence on the NO releasing properties.
Calderone
Vincenzo
V
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy. calderone@farm.unipi.it
Digiacomo
Maria
M
Martelli
Alma
A
Minutolo
Filippo
F
Rapposelli
Simona
S
Testai
Lara
L
Balsamo
Aldo
A
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001565:Benzoates / Q000138:chemical synthesis / Q000494:pharmacology; D001592:Benzyl Alcohols / Q000138:chemical synthesis / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D001565:Benzoates; D001592:Benzyl Alcohols; D002264:Carboxylic Acids; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D011189:Potassium Chloride