Mass spectrometry study of N-alkylbenzenesulfonamides with potential antagonist activity to potassium channels

Abstract

Herein, we report the synthesis and mass spectrometry studies of several N-alkylbenzenesulfonamides structurally related to sulfanilic acid. The compounds were synthesized using a modified Schotten-Baumann reaction coupled with Meisenheimer arylation. Sequential mass spectrometry by negative mode electrospray ionization (ESI(-)-MS/MS) showed the formation of sulfoxylate anion (m/z 65) observed in the mass spectrum of p-chloro-N-alkylbenzenesulfonamides. Investigation of the unexpected loss of two water molecules, as observed by electron ionization mass spectrometry (EI-MS) analysis of p-(N-alkyl)lactam sulfonamides, led to the proposal of corresponding fragmentation pathways. These compounds showed loss of neutral iminosulfane dioxide molecule (M-79) with formation of ions observed at m/z 344 and 377. These ions were formed by rearrangement on ESI(+)-MS/MS analysis. Some of the molecules showed antagonistic activity against Kv3.1 voltage-gated potassium channels.

4-Chloro-3-nitro-N-butylbenzenesulfonamide acts on KV3.1 channels by an open-channel blocker mechanism

“…The voltage pulse protocols and sampling frequency will be described under the particular result. The procedures used for synthesis and chemical characterization of 4-chloro-3-nitro-N-butylbenzenesulfonamide can be found in Martins et al (2016), where it was called compound 3, and references therein.…”

“…Besides this, they were reported to block K V 1.5 channels (Gross et al 2007(Gross et al , 2009Lloyd et al 2007;Olsson et al 2014) and to inhibit K ATP channels in beta cells of the pancreas (Hille 2001). In a previous work we reported the synthesis and chemical characterization of several benzenesulfonamide compounds (Martins et al 2016). Here we report a detailed description of the effects of 4-chloro-3-nitro-N-butylbenzenesulfonamide (SMD2) on K V 3.1 channels.…”