Synthesis of 1,3,4-oxadiazoles derivatives with antidepressant activity and their binding to the 5-HT(1A)receptor
RSC ADVANCES
Authors: Wang, Shiben; Qi, Lin; Liu, Hui; Lei, Kang; Wang, Xuekun; Liu, Renmin
Abstract
In this study, two series of 1,3,4-oxadiazole derivatives were designed and synthesized using the forced swimming test (FST) model to test the antidepressant activity of the target compoundin vivo. Five compounds with potential activity were selected from the FST model to test affinity with 5-HT(1A)receptorin vitro. The results of the FST experiment showed that compoundN-(3-((5-((4-chlorobenzyl)thio)-1,3,4-oxadiazol-2-yl)methoxy)phenyl)acetamide (10g) showed the best antidepressant activity (DID = 58.93, percentage decrease in immobility duration in FST), similar to the activity of positive drug fluoxetine. Compound10galso exhibited the most potent binding affinity to 5-HT(1A)receptors (K-i= 1.52 nM). The results of thein vivo5-HT concentration estimation in mice showed that compound10gmay have an effect on the brain. The experimental results of exploratory activity in mice showed that compound10gdid not affect spontaneous activity in the open-field test model. Molecular docking was used to study the binding mode of compound10gand the 5-HT(1A)receptor. Compound10gshowed significant interactions with residues at the active site on the 5-HT(1A)receptor. The physicochemical and pharmacokinetic properties of the target compounds were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.
Genomic and Transcriptomic Differentiation of Independent Invasions of the Pacific Oyster Crassostrea gigas
FRONTIERS IN ECOLOGY AND EVOLUTION
Authors: Wegner, K. Mathias; Lokmer, Ana; John, Uwe
Abstract
Upon colonizing new habitats, invasive species face a series of new selection pressures as a result of changing abiotic conditions and novel biotic interactions with native species. These new selection pressures can be accommodated by different mechanisms that act on different levels and across different time scales: (1) By changing transcriptomic profiles, species can react by plasticity within individual physiological limitations. (2) Invasive populations can adapt by fixing beneficial genetic variants in response to the newly encountered selection pressures. Here, we compare the genomic and transcriptomic landscapes of two independent invasions of the Pacific Oyster (Crassostrea gigas) into the North Sea. In detail, we combine ddRAD sequencing on the genomic level with RNAseq on the transcriptomic level to reveal outlier loci (SNPs) indicative of adaptation, as well as transcriptomic profiles from a translocation experiment to show immediate physiological reactions between two populations characterizing the two independent invasions. Generally, we found low physical congruence between differentially regulated genes and outlier loci, indicating that different genes are involved on the different time scales. Functionally matching outlier loci and differentially expressed genes were however found for spliceosomal modification of mRNA and particularly for transposon activation, indicating that these variation creating processes might be connected across eco-physiological and evolutionary time scales. By contrasting and identifying functional congruence between population outlier loci and population specific transcriptomic profiles, we can thus reveal a glimpse at the traits and processes characterizing specific mechanisms involved in successful invasions.