RESUMO
KV3.1 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 KV3.1 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 KV3.1, 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 µM; and the Hill coefficient suggests the binding of two molecules to block KV3.1. Also, the effects of all molecules on KV3.1 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 KV3.1 channel blockers.
Assuntos
Ativação do Canal Iônico , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Shaw/antagonistas & inibidores , Sulfonamidas/química , Sulfonamidas/farmacologia , Ácido 4-Aminobenzoico/metabolismo , Animais , Linhagem Celular , Lactamas/metabolismo , Camundongos , Neurônios/metabolismo , Dióxido de Nitrogênio/metabolismo , Bloqueadores dos Canais de Potássio/síntese química , Ácidos Sulfanílicos/metabolismo , Sulfonamidas/síntese química , BenzenossulfonamidasRESUMO
This work investigated the anaerobic degradation of the model azo dye Remazol Yellow Gold RNL in an upflow anaerobic sludge blanket reactor (UASB) and two submerged anaerobic membrane (SAMBR) bioreactors, one of which (SAMBR-1) was operated with powdered activated carbon (PAC) in its interior. The reactors were operated at 35 °C with a hydraulic retention time of 24 h in three operational phases, aimed to assess the effect of external sources of carbon (glucose) or redox mediator (yeast extract) on the removal or color and organic matter. The results showed that removal efficiencies of COD (73-94%) and color (90-94%) were higher for SAMBR-1 when compared to SAMBR-2 (operated without PAC) and UASB reactors. In addition, the presence of PAC in SAMBR-1 increased reactor stability, thereby leading to a lower accumulation of volatile fatty acids (VFA). The microfiltration membrane was responsible for an additional removal of ~50% of soluble residual COD in the form of VFA, thus improving permeate quality. On its turn, PAC exhibited the ability to adsorb byproducts (aromatic amines) of azo dye degradation as well as to act as source of immobilized redox mediator (quinone groups on its surface), thereby enhancing color removal.