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

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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.

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Acknowledgments

The authors would like to thank the Brazilian Research Foundations FAPESP (research fund 2013/24487-6), CNPq and CAPES for their financial assistance. We are also grateful to Post-graduation Program POSMAT at São Paulo State University (UNESP) for the post-graduation fellowship.

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Authors and Affiliations

  1. Laboratório de Química Orgânica Fina, Departamento de Física, Química e Biologia, Faculdade de Ciências e Tecnologia, Universidade Estadual Paulista (UNESP), C.P. 467, Presidente Prudente, SP, 19060-900, Brazil

    Carina C. Martins, Carlos A. Zanutto Bassetto Jr. & Eduardo R. Perez Gonzalez

  2. ThoMSon Mass Spectrometry Laboratory, Institute of Chemistry, University of Campinas, UNICAMP, Campinas, SP, 13083‑970, Brazil

    Jandyson M. Santos & Marcos N. Eberlin

  3. Departamento de Química Inorgânica, Instituto de Química, Universidade de Campinas, UNICAMP, Campinas, 13083-970, SP, Brazil

    Alvicler Magalhães

  4. Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil

    Wamberto Varanda

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  1. Carina C. Martins
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  2. Carlos A. Zanutto Bassetto Jr.
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  3. Jandyson M. Santos
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  4. Marcos N. Eberlin
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  5. Alvicler Magalhães
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Correspondence to Eduardo R. Perez Gonzalez.

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Handling Editor: J. Leban.

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Martins, C.C., Bassetto, C.A.Z., Santos, J.M. et al. Mass spectrometry study of N-alkylbenzenesulfonamides with potential antagonist activity to potassium channels. Amino Acids 48, 445–459 (2016). https://doi.org/10.1007/s00726-015-2099-6

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