AI Article Synopsis
- Novel compounds combining nitric oxide-releasing features with a dorzolamide scaffold were created and tested for their ability to inhibit carbonic anhydrase (CA) enzymes, particularly hCA II.
- Different synthesized compounds showed varying potency levels in inhibiting these enzymes, with compound 8 demonstrating a strong binding affinity confirmed by X-ray crystal structure analysis.
- Compounds 4, 6, and 8 not only effectively relaxed blood vessels but also significantly lowered intraocular pressure in normotensive rabbits, indicating their potential use in treating hypertensive glaucoma.
Article 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.
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| http://dx.doi.org/10.1016/j.bmcl.2009.10.036 | DOI Listing |
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