Three phenothiazine based organic dyes PTA, PDTA and PTDA with D-π-A, π-D-π-A and A-π-D-π-A frameworks were designed and synthesized for the dye sensitized solar cells (DSSCs). Phenothiazine with octyloxyphenyl moiety acts as donor while thiophene and cyanoacetic acid units act as a π-spacer and an acceptor, respectively. The effects of the molecular structures of the dyes on the performance of the DSSCs were investigated systematically along with their photophysical and photoelectrochemical properties. The dye PTDA with A-π-D-π-A framework exhibited a better light harvesting capacity and an effective electron extraction pathway from the electron donor to the TiO2 surface, leading to an efficiency of 6.82% under 100 mW cm? light illumination, while the dyes PTA and PDTA with D-π-A and π-D-π-A frameworks delivered efficiencies of 6.34% and 5.12%, respectively.

We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity mapping revealed homozygous mutations c.484G>A (p.Gly162Arg) and c.1898C>G (p.Pro633Arg) in SLC6A17.SLC6A17 is predominantly expressed in the brain, encodes a synaptic vesicular transporter of neutral amino acids and glutamate, and plays an important role in the regulation of glutamatergic synapses. Prediction programs and 3D modeling suggest that the identified mutations are deleterious to protein function. To directly test the functional consequences, we investigated the neuronal subcellular localization of overexpressed wild-type and mutant variants in mouse primary hippocampal neuronal cells. Wild-type protein was present in soma, axons, dendrites, and dendritic spines. p.Pro633Arg altered SLC6A17 was found in soma and proximal dendrites but did not reach spines. p.Gly162Arg altered SLC6A17 showed a normal subcellular distribution but was associated with an abnormal neuronal morphology mainly characterized by the loss of dendritic spines. In summary, our genetic findings implicate homozygous SLC6A17 mutations in autosomal-recessive intellectual disability, and their pathogenic role is strengthened by genetic evidence and in silico and in vitro functional analyses.

Highlights • Two series of sulfonylcyclic ureas (2a-g and 3a-g) were successfully synthesized. • The compounds were evaluated for hypoglycemic and ARI activity. • Compounds 2b, 2c and 3c were more potent hypoglycemic agents than glibenclamide. • The compounds are more active against aldose reductase than aldehyde reductase. • Compound 2b was found most potent selective inhibitor of ALR2. Abstract A series of 3-arylsulfonylspiroimidazolidine-2,4-diones (2a-g) and their corresponding rearranged products, 1-arylsulfonylspiroimidazolidine-2,4-diones (3a-g) were synthesized and evaluated for antidiabetic and aldose reductase inhibition activity. Three of the compounds (2b, 2c and 3c) were found more potent in-vivo hypoglycemic agents than the commercial drug glibenclamide. The free energy of binding (ΔG) values showed that the compounds are active against aldose reductase and aldehyde reductase enzymes, which was also estimated using molecular mechanics Poisson-Boltzmann surface area method. Of the tested compounds, 2b was found to be the most potent in-vitro selective inhibitor of ALR2 possessing an IC50 value of 0.89 μm. Structure activity relationship and molecular docking revealed the importance of substitution features of aryl group of aryllsulfonylimidazolidine-2,4-dione scaffold. It was observed that the substitution with a halogen at para position of the aryl group had a remarkable effect on ALR2 inhibition potency. Graphical abstract Three of the synthesized sulfonyclyclic urea derivatives were found more potent in-vivo hypoglycemic agents than glibenclamide. In in-vitro ARI assay, the compounds 3a-g were found more ACR1 inhibitors than the standard.

The desired 3-(arylsulfonyl)spiroimidazolidine-2,4-diones were synthesized by reacting spiroiminoimidazolidine-2,4-dione with arylsulfonyl chlorides. Spiroimidazolidine-2,4-dione was in turn synthesized from norcamphor. Structures of the synthesized molecules were established by modern spectroscopic techniques. The synthesized compounds were screened for in vivo antidiabetic activity and aldose reductase inhibition. Compounds 2a, 2b and 2g exhibited excellent dual activity, compound 2a being most prominent. These results reveal that the synthesized compounds may serve as the molecule of choice to treat diabetes and diabetic complications using a single medication.

Ethanol inhibits [125I]calmodulin binding to synaptic plasma membranes from rat brain, and this inhibition is correlated in a conentration-dependent manner with the increase of membrane fluidity, as determined by diphenylhexatriene fluorescence polarization. Moreover, several short-chain alcohols that increase membrane fluidity are also effective inhibitors of [125I]calmodulin binding. These data support the notion that ethanol inhibits calmodulin binding by increasing lipid fluidity of the synaptic membranes.