Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contrast to prediction of above mentioned properties, which can be done with several Internet tools, wide profiling of biological activity can be obtained only with PASS Inet (http://www.ibmc.msk.ru/PASS). PASS Inet was tested by a dozen medicinal chemists for compounds from different chemi...

Computer-aided prediction for medicinal chemistry via the Internet.

This study aimed to investigate the connection between the mutation of the Sip1 transcription factor and impaired Ca2+-signaling, which reflects changes in neurotransmission in the cerebral cortex ...

Interleukin-10 restores glutamate receptor-mediated Ca2+-signaling in brain circuits under loss of Sip1 transcription factor

The alkylation of purine-6-thiol with methallyl chloride and propargyl bromide in aqueous alcohol in the presence of alkali gave 6-[methallyl(propargyl)sulfanyl]purines which reacted with iodine and bromine to afford fused [1,3]thiazolo[2,3-i]purinium systems.

Synthesis of [1,3]Thiazolo[2,3-i]purinium Systems

Introduction: The study aim was to explore a neuroprotective action of magnesium (LKhT-317) and zinc (LKhT-318) taurine salts on experimental models of reperfusion brain damage in rats and cell culture. Materials and methods: The study was performed on male Sprague Dawley rats, and rat’s hippocampal mixed neuroglial cell culture. Magnesium(LKhT-317) and zinc-containing (LKhT-318) derivatives of taurine were studied. Reperfusion brain damage was induced 30 min after intraluminal cerebral middle artery occlusion. Severity of the injury was assessed by local blood flowmetry, neurological symptoms scaling and brain tissue staining. Levels of IL-1b, IL-10 and TNF-alpha in tissue were determined by qualitative ELISA. Caspase-3 and Bcl-2 expressions were detected by IHC. Neurons survival was assessed by cytochemistry. Cellular calcium responses were detected by fluorescent microscopy of Fura-2-containig cells. Results and discussion: Metal-containing taurine derivatives – LKhT-317 and LKhT-318 – demonstrated a sufficient neuroprotective property in rats with a reperfusion-induced brain injury. Both derivatives effectively prevented severity of the animals’ brain damage, motor deficiency, reduction of microvascular perfusion, and proinflammatory cytokines production. Magnesium-containing compound LKhT-317 was comparatively more effective than zinc-containing one. LKhT-317 possessed an anti-apoptotic action in vivo, and protected neurons from OGD-mediated cell death in mixed hippocampal culture. The aforementioned actions may be associated with an LKhT-317 inhibitory effect on NMDA-induced cellular Ca2+ response and, therefore, the anti-excitotoxic property of the compound. Conclusion: Magnesiumand zinc-containing taurine derivatives may be considered as promising neuroprotectors in the reperfusion-induced brain injury.

https://rrpharmacology.pensoft.net/article/59857/download/pdf/

Metal-containing taurine compounds protect rat’s brain in reperfusion-induced injury

This short review provides a general and systematic coverage of literature published since 1961 on the synthesis of [1,3]thiazolo[2,3-i]-, [1,3]thiazino[2,3-i]-, [1,3]thiazolo[3,4,5-gh]-, [1,4]thiazino[4,3,2-gh]purine systems and their hydrogenated derivatives.

Synthesis of Fused Thiazolo- and Thiazinopurine Ring Systems Containing a 6-Thiopurine Moiety

Synthesis of the new heterocyclic system 7,8,9,10-tetrahydrobenzthiazolo[2,3-i]purine

A series of 6-(ω-aroylthio)purines, which have not been described in the literature, has been obtained by the reaction of 6-purinethione with ω-chlorovalerophenone and its substituted derivatives. Some properties of the compounds synthesized have been studied, viz. reaction at the carbonyl group, methylation, and hydrolysis.

Synthesis and some properties of 6-(ω-aroylbutylthio)purines

The effect of a cerebroprotective agent magnesium bis-aminoethanesulfonate (laboratory code FS-LKhT-317) on intracellular calcium concentration was studied by the fluorescent imaging technique on neuroglial cell culture from Spraque-Dawley rat hippocampus. The substance produced a pronounced inhibitory effect and suppressed NMDA receptor activity in concentrations of ≥50 μM. The observed effects were reversible or partially reversible and were detected by a decrease in Ca2+ signal amplitude in neurons in response to NMDA applications in a Mg2+-free medium and by inhibition of Ca2+ pulses in magnesium-free medium (elimination of magnesium block).

Aminoethane Sulfonic Acid Magnesium Salt Inhibits Ca2+ Entry Through NMDA Receptor Ion Channel In Vitro.

Novel anaesthetic formulation LHT-15-32 was studied. The experimental study involved 66 white mice, 15 Rana radibunda frogs and 50 male Sprague Dawley rats. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Tissue IL-1β, IL-10 and TNF-a concentration was quantitatively assessed by ELISA. LHT-15-32 Na-blocking activity was studied on isolated neurons of Limnea stagnalis para-pharyngeal ganglion. Rana radibunda isolated sciatic nerve was perfused with LHT-15-32 to assess its conductivity. LHT-15-32 acute intravenous and subcutaneous toxicity was lower then that of its active substance LHT-4-00. The formulation infraorbital administration induced deep dental anaesthesia lasted longer than 70 min, activated local antioxidant defence system and decreased IL-1β level in gingival tissue. At 10-6 to 10-3 M LHT-15-32 inhibited sciatic nerve conductivity and blocked Na+-channels of isolated neurons in dose-dependent manner. LHT-15-32 proved to be less toxic than active substance and lidocaine. The agent provides deep and prolonged anesthesia of the upper molar of rats in chronic apical periodontitis, lowers tissue concentration of pain cascade cytokines and oxidative stress activity and suppresses the action potential amplitude of a sensory nerve due to Na-blocking activity.

[Experimental study of the effectiveness of local anesthetic activity of a new dimethylphenylacetamide-containing pharmaceutical composition in chronic periodontitis].

S. Ya. Skachilova

Papers

Synthesis of the new heterocyclic system 7,8,9,10-tetrahydrobenzthiazolo[2,3-i]purine

Synthesis and some properties of 6-(ω-aroylbutylthio)purines

Aminoethane Sulfonic Acid Magnesium Salt Inhibits Ca2+ Entry Through NMDA Receptor Ion Channel In Vitro.

[Experimental study of the effectiveness of local anesthetic activity of a new dimethylphenylacetamide-containing pharmaceutical composition in chronic periodontitis].

Synthesis and Antiarrhythmic Activity of 2-Diethylamino-21,61-dimethylphenylacetamide Derivatives (I).