Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential anti-inflammatory properties

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Chisté, RC (Author) Other; Ribeiro, D (Author) Other; Freitas, M (Author) Other; Leite, A (Author) Other; Moniz, T (Author) Other; Maria Rangel (Author) ICBAS; Fernandes, E (Author) FFUP

Journal

Title: Journal of Inorganic Biochemistry

Vol. 155

Pages: 9-16

ISSN: 0162-0134

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-00G-WRB

DOI: 10.1016/j.jinorgbio.2015.11.009

Abstract (EN): Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (Hmpp) or two methyl groups (Hdmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15 mu M. Among all the compounds, [Cu(mpp)(2)] and [Cu(dmpp)(2)] exhibited the highest scavenging capacity against superoxide radical (O-2(center dot-)) (IC50 = 0.36 +/- 0.07 and 0.30 +/- 0.06 M, respectively) and against hypochlorous acid (HOCl) (IC50 = 0.6 +/- 0.3 and 0.4 +/- 0.1 mu M, respectively). In the particular case of O-2(center dot-), [Fe(mpp)(3)] and [Fe(dmpp)(3)] (both at 15 mu M) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O-2(center dot-) nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6-39%). Finally, with exception of [VO(mpp)(2)] and [VO(dmpp)(2)], all compounds exhibited scavenging activity against HOCl (39-81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as an useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8