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Issue 18, 2010
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Acyclic triaryl olefins possessing a sulfohydroxamic acid pharmacophore: synthesis, nitric oxide/nitroxyl release, cyclooxygenase inhibition, and anti-inflammatory studies

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Abstract

Nitric oxide (NO) and its reduced form nitroxyl (HNO), effective vasodilation agents that can inhibit platelet aggregation and adhesion, could suppress adverse cardiovascular effects associated with the use of selective COX-2 inhibitors. In this regard, a sulfohydroxamic acid (SO2NHOH) substituent, that can act as a dual NO/HNO donor moiety, was inserted at the para-position of the C2 phenyl ring of acyclic 2-alkyl-1,1,2-triaryl olefins previously shown to be potent and highly selective COX-2 inhibitors. Although this new group of 1,1-diaryl-2-(4-hydroxyaminosulfonylphenyl)alk-1-enes exhibited weak inhibition of the constitutive cyclooxygenase-1 (COX-1) and inducible COX-2 isozymes, in vivo studies showed anti-inflammatory potencies that were generally intermediate between that of the reference drugs aspirin and ibuprofen. All compounds released NO (5.6–13.5% range) upon incubation with phosphate buffer which was increased further (8.3–25.6% range) in the presence of the oxidant K3(FeCN6).The low release of HNO in MeOH-buffer (< 2% at 24 h incubation) was much higher at alkaline pH (11–37% range). The concept of designing better anti-inflammatory drugs possessing either an effective HNO, or dual NO/HNO, donor moiety that are devoid of adverse ulcerogenic and/or cardiovascular side effects warrants further investigation.

Graphical abstract: Acyclic triaryl olefins possessing a sulfohydroxamic acid pharmacophore: synthesis, nitric oxide/nitroxyl release, cyclooxygenase inhibition, and anti-inflammatory studies

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Publication details

The article was received on 13 Apr 2010, accepted on 17 Jun 2010 and first published on 22 Jul 2010


Article type: Paper
DOI: 10.1039/C005066K
Org. Biomol. Chem., 2010,8, 4124-4130

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    Acyclic triaryl olefins possessing a sulfohydroxamic acid pharmacophore: synthesis, nitric oxide/nitroxyl release, cyclooxygenase inhibition, and anti-inflammatory studies

    Z. Huang, C. Velázquez, K. Abdellatif, M. Chowdhury, S. Jain, J. Reisz, J. DuMond, S. B. King and E. Knaus, Org. Biomol. Chem., 2010, 8, 4124
    DOI: 10.1039/C005066K

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