| Full text | |
| Author(s): |
Zanutto Bassetto Junior, Carlos Alberto
[1]
;
Gushiken Passianoto, Luana Vitorino
[1]
;
Perez Gonzalez, Eduardo Rene
[1]
;
Varanda, Wamberto Antonio
[2]
Total Authors: 4
|
| Affiliation: | [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
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Amino Acids; v. 51, n. 2, p. 355-364, FEB 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 12/19750-7 - Nitric oxide as a modulator of electrical activity in magnocellular neurons of the rat supraoptic nucleus |
| Grantee: | Wamberto Antonio Varanda |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/24487-6 - Study of reactions of clean synthesis and chemical modification of the biodiesel and fusel oil for preparation of organic carbonate and carbamates using carbon dioxide in the presence of organocatalysts and heterogeneous catalysts |
| Grantee: | Eduardo Rene Perez Gonzalez |
| Support Opportunities: | Regular Research Grants |