Design, Synthesis and Evaluation of Novel Trichloromethyl Dichlorophenyl Triazole Derivatives as Potential Safener

The dominance of safener can unite with herbicides acquiring the efficient protection of crop and qualifying control of weeds in agricultural fields. In order to solve the crop toxicity problem and exploit the novel potential safener for fenoxaprop-P-ethyl herbicide, a series of trichloromethyl dichlorobenzene triazole derivatives were designed and synthesized by the principle of active subunit combination. A total of 21 novel substituted trichloromethyl dichlorobenzene triazole compounds were synthesized by substituted aminophenol and amino alcohol derivatives as the starting materials, using cyclization and acylation. All the compounds were unambiguously characterized by IR, 1H-NMR, 13C-NMR, and HRMS. A greenhouse bioassay indicated that most of the title compounds could protect wheat from injury caused by fenoxaprop-P-ethyl at varying degrees, in which compound 5o exhibited excellent safener activity at a concentration of 10 μmol/L and was superior to the commercialized compound fenchlorazole. A structure–activity relationship for the novel compounds was determined, which demonstrated that those compounds containing benzoxazine groups showed better activity than that of oxazole-substituted compounds. Introducing a benzoxazine fragment and electron-donating group to specific positions could improve or maintain the safener activity for wheat against attack by the herbicide fenoxaprop-P-ethyl. A molecular docking model suggested that a potential mechanism between 5o and fenoxaprop-P-ethyl is associated with the detoxication of the herbicide. Results from the present work revealed that compound 5o exhibited good crop safener activities toward wheat and could be a promising candidate structure for further research on wheat protection.

Tuning the tetraethylammonium sensitivity of potassium channel Kcv by subunit combination

Tetraethylammonium (TEA) is a potassium (K+) channel inhibitor that has been extensively used as a molecular probe to explore the structure of channels’ ion pathway. In this study, we identified that Leu70 of the virus-encoded potassium channel Kcv is a key amino acid that plays an important role in regulating the channel’s TEA sensitivity. Site-directed mutagenesis of Leu70 can change the TEA sensitivity by 1,000-fold from ∼100 µM to ∼100 mM. Because no compelling trends exist to explain this amino acid’s specific interaction with TEA, the role of Leu70 at the binding site is likely to ensure an optimal conformation of the extracellular mouth that confers high TEA affinity. We further assembled the subunits of mutant and wt-Kcv into a series of heterotetramers. The differences in these heterochannels suggest that all of the four subunits in a Kcv channel additively participate in the TEA binding, and each of the four residues at the binding site independently contributes an equal binding energy. We therefore can present a series of mutant/wild-type tetramer combinations that can probe TEA over three orders of magnitude in concentration. This study may give insight into the mechanism for the interaction between the potassium channel and its inhibitor.

Association between the HMW-glutenin subunits and gluten strength characteristics in khorassan wheat lines - Short Communications

Khorassan wheat (Triticum turgidum ssp. turanicum Jakubz em. A. Löve & D. Löve) is an ancient tetraploid wheat that was grown in the Mediterranean region and Near East. Sixteen lines differing in the composition of high-molecular-weight glutenin subunits (HMWGs) were evaluated for SDS-sedimentation volume and quality index (QI). The data suggested that the two subunit combinations detected in the examined materials at the Glu-B1 locus showed differences in both characteristics (relatively higher levels at the presence of the subunit combination 7+15 compared to 6+8). Weak gluten is in general characteristic of this wheat species. It could be used in a better way for other baking applications than for the pasta industry.

Activation of Nicotinic Acetylcholine Receptors Increases the Frequency of Spontaneous GABAergic IPSCs in Rat Basolateral Amygdala Neurons

The basolateral amygdala (BLA) is a critical component of the amygdaloid circuit, which is thought to be involved in fear conditioned responses. Using whole cell patch-clamp recording, we found that activation of nicotinic acetylcholine receptors (nAChRs) leads to an action potential-dependent increase in the frequency of spontaneous GABAergic currents in principal neurons in the BLA. These spontaneous GABAergic currents were abolished by a low-Ca2+/high-Mg2+ bathing solution, suggesting that they are spontaneous inhibitory postsynaptic currents (sIPSCs). Blockade of ionotropic glutamate receptors did not prevent this increased frequency of sIPSCs nor did blockade of α7 nAChRs. Among the nAChR agonists tested, cystisine was more effective at increasing the frequency of the sIPSCs than nicotine or 1,1-dimethyl-4-phenyl piperazinium iodide, consistent with a major contribution of β4 nAChR subunits. The nicotinic antagonist, dihydro-β-erythroidine, was less effective than d-tubocurarine in blocking the increased sIPSC frequency induced by ACh, suggesting that α4-containing nAChR subunits do not play a major role in the ACh-induced increased sIPSC frequency. Although α2/3/4/7 and β2/4 nAChR subunits were found in the BLA by RT-PCR, the agonist and antagonist profiles suggest that the ACh-induced increase in sIPSC frequency involves predominantly α3β4-containing nAChR subunits. Consistent with this, α-conotoxin-AuIB, a nAChR antagonist selective for the α3β4 subunit combination, inhibited the ACh-induced increase in the frequency of sIPSCs. The observations suggest that nicotinic activation increases the frequency of sIPSCs in the BLA by acting mainly on α3β4-containing nicotinic receptors on GABAergic neurons and may play an important role in the modulation of synaptic transmission in the amygdala.

Functional Excitatory Synapses in HEK293 Cells Expressing Neuroligin and Glutamate Receptors

The discovery that neuroligin is a key protein involved in synapse formation offers the unprecedented opportunity to induce functional synapses between neurons and heterologous cells. We took this opportunity recording for the first-time synaptic currents in human embryonic kidney 293 (HEK293) cells transfected with neuroligin and the N-methyl-d-aspartate or AMPA receptor subunits in a co-culture with rat cerebellar granule cells. These currents were similar to synaptic currents recorded in neurons, and their decay kinetics was determined by the postsynaptic subunit combination. Although neuroligin expression was sufficient to detect functional synapses, cotransfection of HEK293 cells with Postsynaptic density-95/synapse-associated protein-90 (PSD-95) significantly increased current frequency. Our results support the central role of neuroligin in the formation of CNS synapses, validate the proposal that PSD-95 allows synaptic maturation, and provide a unique experimental model to study how molecular components determine functional properties of excitatory synapses.