An efficient synthesis of simple β,β'-cyclobisalkylated melatoninergic phenylalkylamides

Treatment of the commercially available 3-methoxyphenylacetonitrile (6) with sodium bis (trimethylsilyl)amide and subsequent cyclobisalkylation with α,ω-dibromo or dichloroalkanes in THF at 0 °C produces adducts 7a-d, which serve as precursors to the new conformationally constrained phenylalkylamides 5a-h. Compounds 5a-f are melatonin receptor agonists in the Xenopus laevis melanophore assay and their potency depends on both the size of the R group and the size and shape of the β-substituent. The fact that the cyclohexano-substituted analogs 5g and 5h are, regardless of the size of the R group, melatonin receptor antagonists, implies that the nature of the β-substituent constitutes a functional probe in the receptor's dynamic agonist-antagonist conformational equilibrium. © 2007 Bentham Science Publishers Ltd

The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate release region dependently

Cannabinoid administration modulates both dopaminergic and glutamatergic neurotransmission. The present study examines the effects of high and low dose WIN55,212-2, a CB1 receptor agonist, on extracellular dopamine and glutamate release in vivo via brain microdialysis in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) in parallel to its effects on locomotor activity. WIN55,212-2 increased extracellular dopamine in the NAc (1Â mg/kg i.p.), striatum (0.1 and 1Â mg/kg i.p.) and PFC (1Â mg/kg i.p.). Glutamate release was also elevated by WIN55,212-2 in the PFC (1Â mg/kg i.p.) whereas in the NAc (0.1 and 1Â mg/kg i.p.) and striatum, it was reduced (1Â mg/kg i.p.). WIN55,212-2 administration produced hyperlocomotion at the lower dose (0.1Â mg/kg i.p.) and hypolocomotion at the higher dose (1Â mg/kg i.p.). Co-Administration with the CB1 antagonist, SR-141716A (0.03Â mg/kg i.p.), prevented the above effects. According to the present results, WIN55,212-2 affected locomotor activity biphasically while exerting converging effects on dopamine activity but diverging effects on glutamate release between cortical and subcortical regions, especially at the higher dose. These findings emphasize the involvement of the CB1 receptor in the simultaneous modulation of dopaminergic and glutamatergic neurotransmission in brain regions involved in reward and locomotion and suggest possible underlying mechanisms of acute cannabinoid exposure and its psychoactive and behavioural manifestations. © CINP 2012

Cannabinoids negatively modulate striatal glutamate and dopamine release and behavioural output of acute d-amphetamine

The cannabinoid system plays a regulatory role in neurotransmission and is involved in the central actions of psychostimulants. This complex interaction between the cannabinoid system and psychostimulants represents a potential pharmacological target for psychosis and addiction. However, most studies have focused on cocaine, therefore, it is unclear whether these findings can be extended to other psychostimulants such as the amphetamines. The present study investigated the effects of WIN55,212-2, a synthetic cannabinoid and SR141716A, a CB1 receptor antagonist, on d-amphetamine-induced locomotor activity and extracellular dopamine and glutamate release in the striatum. Rats were either observed for locomotor activity or glutamate and dopamine neurotransmitter release in the striatum using in vivo microdialysis following intraperitoneal co-administration of d-amphetamine with WIN55,212-2 or SR141716A. Our results demonstrated that d-amphetamine per se induced hyperlocomotion and enhanced dopamine and glutamate release, as expected. WIN55,212-2 dampened these effects when co-administered with d-amphetamine, while alone it displayed its characteristic biphasic motor profile coupled with increases in dopamine and decreases in glutamate release. SR141716A at high doses reduced d-amphetamine-induced hyperlocomotion and completely reversed enhanced dopamine and glutamate release but alone had no effect. These findings validate the capacity of the cannabinoid system to modulate amphetamine-induced behaviour and its neurochemical output, in a state-dependent manner, providing insight into aspects of the neurobiological substrate that underlies amphetamines' psychotogenic and addictive properties. © 2014 Elsevier B.V

Oil-in-water microemulsions as hosts for benzothiophene-based cytotoxic compounds: An effective combination

Targeted delivery of chemotherapeutics in order to overcome side effects and enhance chemosensitivity remains a major issue in cancer research. In this context, biocompatible oil-in-water (O/W) microemulsions were developed as matrices for the encapsulation of DPS-2 a benzothiophene analogue, exhibiting high cytotoxicity in various cancer cell lines, among them the MW 164 skin melanoma and Caco-2 human epithelial colorectal adenocarcinoma cell lines. The microemulsion delivery system was structurally characterized by dynamic light scattering (DLS) and electron paramagnetic resonance (EPR) spectroscopy. The effective release of a lipophilic encapsulated compound was evaluated via confocal microscopy. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay. When encapsulated, DPS-2 was as cytotoxic as when dissolved in dimethyl sulfoxide (DMSO). Hence, the oil cores of O/W microemulsions were proven effective biocompatible carriers of lipophilic bioactive molecules in biological assessment experiments. Further investigation through fluorescence-activated cell sorting (FACS) analysis, comet assay, and Western blotting, revealed that DPS-2, although non-genotoxic, induced S phase delay accompanied by cdc25A degradation and a nonapoptotic cell death in both cell lines, which implies that this benzothiophene analogue is a deoxyribonucleic acid (DNA) replication inhibitor. © 2018 by the authors

Total synthesis of amphoteronolide B and amphotericin B. 1. Strategy and stereocontrolled construction of key building blocks

This article does not have an abstract

Studies on the thermotropic effects of cannabinoids on phosphatidylcholine bilayers using differential scanning calorimetry and small angle X-ray diffraction

Journal URL: http://www.sciencedirect.com/science/journal/0005273

Addendum: Oil-In-Water microemulsions as hosts for benzothiophene-based cytotoxic compounds: An effective combination. [Biomimetics, 3, 13, (2018)] DOI: 10.3390/biomimetics3040033

It was brought to our attention that due to recent changes in the regulation that governs the Ph.D. program at the University of Thessaly, it is mandatory to state the academic institution the Ph.D. student is affiliated with. This was omitted in [1], and we would like to add the following information to the affiliation line for the first author, Ioanna Theochari: "Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece". Line numbers within the affiliation section have been rearranged and changed as follows: Ioanna Theochari 1, Vassiliki Papadimitriou 1, Demetris Papahatjis 1, Nikos Assimomytis 1, Efthimia Pappou 1, Harris Pratsinis 2, Aristotelis Xenakis 1 and Vasiliki Pletsa 1,* 1 Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece; [email protected] (I.T.); [email protected] (V.Pa.); [email protected] (D.P.); [email protected] (N.A.); [email protected] (E.P.); [email protected] (A.X.) 2 Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre of Scientific Research "Demokritos", 11635 Athens, Greece; [email protected] * Correspodence: [email protected]; Tel.: +302-107-273-7541 has been corrected to Ioanna Theochari 1,2, Vassiliki Papadimitriou 1, Demetris Papahatjis 1, Nikos Assimomytis 1, Efthimia Pappou 1, Harris Pratsinis 3, Aristotelis Xenakis 1 and Vasiliki Pletsa 1,* 1 Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece; [email protected] (I.T.); [email protected] (V.Pa.); [email protected] (D.P.); [email protected] (N.A.); [email protected] (E.P.); [email protected] (A.X.) 2 Department of Biochemistry and Biotechnology, School of Health Sciences, University of Thessaly, Viopolis, 41500 Larissa, Greece 3 Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre of Scientific Research "Demokritos", 11635 Athens, Greece; [email protected] * Correspodence: [email protected]; Tel.: +302-107-273-7541. We apologize for any inconvenience this may have caused. The change does not affect the scientific results. The manuscript will be updated and the original will remain online on the article website, with a reference to this addendum. © 2018 by the authors