Nω-NITRO- Nω'-SUBSTITUTED GUANIDINES: A SIMPLE CLASS OF NITRIC OXIDE SYNTHASE INHIBITORS

Christophe D Guillon; David D Wisnoski; Jaya Saxena; Ned D Heindel; Diane E Heck; Donald J Wolff; Jeffrey D Laskin

doi:10.4236/mri.2014.32006

N^ω-NITRO- N^ω'-SUBSTITUTED GUANIDINES: A SIMPLE CLASS OF NITRIC OXIDE SYNTHASE INHIBITORS

Mod Res Inflamm. 2014 May;3(2):48-58. doi: 10.4236/mri.2014.32006.

Authors

Christophe D Guillon¹, David D Wisnoski¹, Jaya Saxena¹, Ned D Heindel¹, Diane E Heck², Donald J Wolff³, Jeffrey D Laskin⁴

Affiliations

¹ Department of Chemistry, Lehigh University, 6 East Packer Avenue, Bethlehem, PA, USA.
² Department of Environmental Health Science, New York Medical College, Valhalla, NY, USA.
³ Department of Pharmacology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ, USA.
⁴ Department of Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Abstract

A series of N^ω-nitro-N^ω'-substituted guanidines has been prepared as potential inhibitors of the human Nitric Oxide Synthase (NOS) isoforms. The reported utility of aminoguanidine and nitroarginine in iNOS inhibition points to a potential similar utility for analogs of nitro-guanidine. The compound library was tested against the three isoforms of Nitric Oxide Synthase (eNOS, iNOS and nNOS). Several candidates showed excellent activity and good selectivity for nNOS. One particular compound even demonstrated good selectivity for iNOS. The potential usefulness of such selective inhibitors is discussed.

Keywords: Nitric Oxide Synthase (NOS); Nitro-guanidines; isoforms; selective inhibitors.

Grants and funding

U54 AR055073/AR/NIAMS NIH HHS/United States