| Literature DB >> 19854054 |
Rebecca M Steele1, Francesca Benedini, Stefano Biondi, Valentina Borghi, Laura Carzaniga, Francesco Impagnatiello, Daniela Miglietta, Wesley K M Chong, Ranjan Rajapakse, Alessandro Cecchi, Claudia Temperini, Claudiu T Supuran.
Abstract
Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma.Entities:
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Year: 2009 PMID： 19854054 DOI： 10.1016/j.bmcl.2009.10.036
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823