Mechanism of Thiol-Induced Nitrogen(II) Oxide Donation by Furoxans: a Quantum-Chemical Study

A Focused Library of NO‐Donor Compounds with Potent Antiproliferative Activity Based on Green Multicomponent Reactions

“…Among nitric oxide releasing moieties, furoxan has attracted considerable attention due to its stability under ambient conditions and ability to produce large fluxes of NO by a thiol‐dependent mechanism, thereby eliciting the cytotoxic effects associated with NO. Unlike organic nitrates, furoxans do not promote tolerance under continuous therapy . Organic nitrates are the oldest and structurally simplest NO‐donor with an important role in cardiovascular therapy but also have demonstrated anticancer properties in vitro and in vivo .…”

“…Unlike organic nitrates,f uroxansd on ot promote tolerance under continuous therapy. [31,41] Organicn itrates are the oldest and structurally simplest NO-donorw ith an important role in cardiovascular therapy but also have demonstrated anticancer properties in vitro and in vivo. [42] Many efforts have been made to fully elucidate the mechanism of NO generation by organic nitrates.…”

“…9, 11.4 ppm;M S( EI, 70 eV): m/z (%) 621 (M + ÀBoc-Cyclohexyl, 2), 481 (M + ÀBoc-furoxanyl,15), 360(15), 342(26), 205(36), 121 (100), 83(33), 77 (70), 56(20);H RMS: m/z calcd for C41 H 47 N 3 O 12 SNa:8 28.2778 [M + Na] + , found:828.2784. 1-[6-(tert-butoxycarbonyl)oxy-2,5,7,8-tetramethylchroman-2-yl]-1-(pentylaminocarbonyl)methyl 3-(3-phenylsulfonyl-[1,2,5]oxadiazol-4-yl N 2 -oxide)oxybenzoate (4 i):T his compound was obtained by method A.…”

Selective Methylmagnesium Chloride Mediated Acetylations of Isosorbide: A Route to Powerful Nitric Oxide Donor Furoxans

“…Furoxans have long been known to release NO upon reaction with thiols, including cysteine. 12 DFT calculations supported the addition of a sulfanyl radical onto the C=N bond of the furoxan followed by expulsion of NO, 27 although others give alternative thiolate addition mechanisms, 12,14 which are energetically less favourable. 27 NO-release holds a reasonable correlation with vascular tissue relaxation in a series of furoxans.…”

“…12 DFT calculations supported the addition of a sulfanyl radical onto the C=N bond of the furoxan followed by expulsion of NO, 27 although others give alternative thiolate addition mechanisms, 12,14 which are energetically less favourable. 27 NO-release holds a reasonable correlation with vascular tissue relaxation in a series of furoxans. 11,12 NO is, however, never measured directly due to very rapid oxidation in aqueous and biological fluids to nitrite (NO2 -) and nitrate (NO3 -).…”