Benzenesulfonamides act as open-channel blockers on K(V)3.1 potassium channel

Autor(es)

Zanutto Bassetto Junior, Carlos Alberto ^[1] ; Gushiken Passianoto, Luana Vitorino ^[1] ; Perez Gonzalez, Eduardo Rene ^[1] ; Varanda, Wamberto Antonio ^[2]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ Unesp Campus Presidente Prud, Fac Sci & Technol, Fine Organ Chem Lab, Dept Chem & Biochem, BR-19060900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Amino Acids; v. 51, n. 2, p. 355-364, FEB 2019.
• Citações Web of Science: 0

Resumo

K(V)3.1 blockers can serve as modulators of the rate of action potential firing in neurons with high rates of firing such as those of the auditory system. We studied the effects of several bioisosteres of N-alkylbenzenesulfonamides, and molecules derived from sulfanilic acid on K(V)3.1 channels, heterologously expressed in L-929 cells, using the whole-cell patch-clamp technique. Only the N-alkyl-benzenesulfonamides acted as open-channel blockers on K(V)3.1, while molecules analogous to PABA (p-aminobenzoic acid) and derived from sulfanilic acids did not block the channel. The IC50 of six N-alkyl-benzenesulfonamides ranged from 9 to 55 mu M; and the Hill coefficient suggests the binding of two molecules to block K(V)3.1. Also, the effects of all molecules on K(V)3.1 were fully reversible. We look for similar features amongst the molecules that effectively blocked the channel and used them to model a blocker prototype. We found that bulkier groups and amino-lactams decreased the effectiveness of the blockage, while the presence of NO2 increased the effectiveness of the blockage. Thus, we propose N-alkylbenzenesulfonamides as a new class of K(V)3.1 channel blockers. (AU)

• Processo FAPESP: 12/19750-7 - Óxido nítrico como modulador da atividade elétrica de neurônios magnocelulares do núcleo supraóptico do rato
• Beneficiário: Wamberto Antonio Varanda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/24487-6 - Estudo de reações de síntese limpa e modificação química do biodiesel e óleo fúsel para preparação de carbonatos e carbamatos orgânicos utilizando dióxido de carbono na presença de organocatalisadores e catalisadores heterogêneos
• Beneficiário: Eduardo Rene Perez Gonzalez
• Modalidade de apoio: Auxílio à Pesquisa - Regular